bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceived value of cancer survivorship care among Asians and Native Hawaiian/Pacific Islanders.
Authors: Acoba Jared David , Tamashiro Sharon , Chock Marci 
Published: May 2020

e22522 Background: Numerous studies have evaluated the impact of cancer survivorship care. However, no study to date has focused on Asian or Native Hawaiian/Pacific Islander (NH/PI) cancer survivors. It has been well documented that Asian and NH/PI patients often suffer from inferior cancer outcomes compared to White patients, and differences in their experience with cancer survivorship care could contribute to this disparity. Methods: Surveys were sent to 1410 cancer survivors who were treated at a community cancer center with curative intent and who had received survivorship care plans between Jan 2014 and June 2018. The 26-item questionnaire evaluated patients’ perception of various aspects of their survivorship care plan and follow-up physician visits. All responses were anonymous. Results: Of the 360 patients who responded, 24% were White, 54% Asian, and 13% NH/PI. Compared to Whites, Asian and NH/PI patients were younger (p = 0.004), less educated (p = 0.004), and reported a lower income (p < 0.0005). Among all patients, 62% reported that the survivorship care plan was “very helpful” and 86% rated their satisfaction with physician follow-up visits as “very good” to “excellent.” There were no racial differences in satisfaction with either survivorship care plan or physician follow-up. In a multivariate binary logistic regression, Asians and NH/PI patients were significantly more likely to rate ongoing survivorship care as helpful compared to Whites, OR 4.08 (95%CI, 2.13-7.82). Conclusions: There were no racial differences in patient satisfaction with their survivorship care plans and follow-up care. However, Asian and NH/PI patients valued ongoing cancer survivorship care follow-up significantly more than White patients. Whether more extensive survivorship care would lead to improved outcomes among Asian and NH/PI cancer patients should be investigated further.
Effect of FAmily CEntered (FACE) advance care planning (ACP) on families’ appraisals of caregiving for their teens with cancer.
Authors: Baker Justin N. , Thompkins Jessica , Friebert Sarah , Needle Jennifer , Wang Jichuan , Cheng Yao , Lyon Maureen 
Published: May 2020

e22533 Background: Little is known about how well family caregivers respond to participating in pACP. The research objective was to understand the effect of FAmily CEntered pediatric Advance Care Planning (FACE pACP) for teens with cancer (FACE-TC) on families’ appraisals of caregiving for their child over time. Methods: 126 adolescent/family dyads were randomized to either FACE-TC intervention or treatment as usual control. FACE-TC is three weekly, 60-minute pACP sessions with a trained/certified facilitator. Family Appraisal of Caregiving Questionnaire subscales assessed outcomes. Generalized Estimating equations (GEE) model was used to examine outcome change over time. The effect of intervention on the change was examined by the interaction between time and intervention. Results: 126 adolescent/family dyads completed baseline assessments. 102 dyads completed the 3-month assessment. Adolescents were mean age of 17 years (range 14-20); 57% female; 79% Caucasian. Family participants were mean age 46 (range 19-67); 83% female; 82% Caucasian. Positive caregiving appraisals subscale items are “Caring for __ is satisfying; It is a privilege to care for __; Caring for __ has made me feel closer to him/her; I am able to comfort __ when he/she needs it; I feel confident I can handle most problems in caring for __; I feel useful in my relationship with __; I am committed to caring for __”. FACE pACP significantly increased positive caregiving appraisals at 3 months post-intervention, compared to controls, (β = 0.20, Confidence Interval = 0.03-0.37, p = 0.0189). No significant differences were found between groups for the subscales: burden, distress or family well-being. Conclusions: FACE pACP significantly increased positive caregiver appraisals compared to controls. The family caregiver’s role is critical for the well-being of teens with cancer. Findings identified positive aspects of caregiving in the context of pACP without increasing caregiver burden or distress. Clinical trial information: NCT02693665.
Preliminary safety, pharmacokinetics, and efficacy results from an open-label, multicenter, Phase I/II study of avapritinib in Chinese patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).
Authors: Li Jian , Gong Jifang , Wang Xicheng , Li Jie , Li Yan , QI Changsong , Shen Lin , Ren Wenxiao , Zhao Wanqi , Wang Yedong , Hu Jin , Ren Chunli , Song Wenjie , Yang Jianxin 
Published: May 2020

e23526 Background: More than 85% of GIST patients (pts) have tumors associated with KIT or PDGFRA mutations. Avapritinib is a potent, selective, small-molecule inhibitor that targets KIT/PDGFRA activation loop mutants. Recently FDA approved avapritinib for pts with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including D842V mutations based on a robust ORR (84%) in the NAVIGATOR study. This abstract reports preliminary results from the dose escalation part of the bridging study in Chinese pts with advanced GIST. Methods: Adult pts with unresectable or metastatic GIST that progressed after imatinib and ≥ 1 other tyrosine kinase inhibitor, or could not tolerate the standard treatment or had PDFGRA D842V mutation were enrolled and treated with avapritinib once daily (QD) in continuous 28-day cycles following a modified 3+3 dose escalation design. Primary objectives included determination of Recommended Phase II dose (RP2D) and assessment of safety. PK parameters and response per mRECIST v1.1 for GIST were also assessed. Results: As of 25 Dec 2019, 12 pts were treated with avapritinib QD at a starting dose of 200 mg or 300 mg (6 per group). No dose-limiting toxicities were observed. Most treatment-emergent adverse events (TEAEs) were Grade (G) 1-2, most commonly blood creatine phosphokinase increased (n = 9) and blood bilirubin increased (n = 8). There were no G4-5 TEAEs. The most frequent G3 treatment-related TEAE was anaemia (n = 2). Serious adverse events were observed in 1 pt (renal hydrocele) in 200 mg group and 2 pts (abdominal distension and anaemia) in 300 mg group, all were G3 and considered unrelated to avapritinib. No AEs leading to drug discontinuation occurred. Avapritinib was rapidly absorbed (median Tmax 2.0-4.0 h) and the exposure increased proportionally with doses at the steady state. The mean half-life of avapritinib ranged 42.2-44.4 h, supporting QD dosing. Of the 3 pts with PDGFRA D842V mutation (all in the 300 mg group), 2 pts achieved PR, and 1 had SD, as assessed by investigators at the first tumor assessment. Conclusions: Avapritinib appears generally tolerable at 200 mg and 300 mg QD and shows clinical activity in Chinese pts with PDGFRA D842V mutation. Based on the safety profile in Chinese pts and dose selection results in NAVIGATOR study, 300 mg QD was determined to be the RP2D for Chinese pts. The preliminary safety, PK, and efficacy data support further investigation of avapritinib in Chinese pts with GIST. Clinical trial information: NCT04254939 .
The potential role of extracellular matrix in the activity of trabectedin.
Authors: De Vita Alessandro , Recine Federica , Miserocchi Giacomo , Pieri Federica , Farnedi Anna , Fabbri Francesco , Fausti Valentina , Liverani Chiara , Spadazzi Chiara , Cocchi Claudia , Casadei Roberto , Ercolani Giorgio , Riva Nada , Gurrieri Lorena , Ibrahim Toni , Mercatali Laura 
Published: May 2020

e23542 Background: Soft tissue sarcomas (sts) represent a rare group of solid neoplasm of mesenchymal origin with a 1% incidence of all adult cancers. Liposarcoma and leiomyosarcoma (L-sarcoma) are the most common histotypes. The current first-line treatment for advanced/metastatic L-sarcomas is represented by anthracycline based-regimens. Second-line therapy options include trabectedin, eribulin, ifosfamide, gemcitabine and dacarbazine. In particular, the activity of trabectedin, a tetrahydroisoquinoline molecule, as well as its mechanism of action is not completely elucidated. Methods: The study involved six patient affected L-sarcoma. Patient-derived primary cultures were established after patient surgical treatment. Primary cells were cultured in standard monolayer culture and 3D collagen-based scaffolds. In order to gain inside into the mechanism of action of the drugs, genomic-, chemobiogram, proteomic-, cytometer and in silico analysis were performed. Results: The results confirmed the preservation of tumor gene expression in 3D culture model compared to standard monolayer culture. In particular 3D culture system was able to resemble the patient gene expression of TGFb, SLUG, SNAIL, MMP9 compared to 2D. In silico analysis showed an upregulation of COL1A1 gene, the extracellular matrix component of the present 3D model, in sts compared to other tumors. Pharmacological analysis displayed an increased sensitivity to trabectedin in all the 3D L-sarcoma primary culture compared to 2D culture system, while this was not observed with the other drugs. As previous preclinical evidences suggested that trabectedin mechanism of action include the impairing of ECM proteolytic degradation mediated by tumor cells, we think that its high observed sensitivity depend on the presence of collagen in our 3D- model. Conclusions: These results were suggestive of the losing credibility of monolayer standard culture for pharmacology studies and highlight the promising role of 3D patient-derived culture model for the study of sts biology. Moreover these results shed the light on the potential role of ECM in the mechanism of action of trabectedin in L-sarcomas. The work points out the role of this tumor microenvironment component in predicting response to trabectedin and provide the rationale for better stratifying patients which will be candidate for this drug. Further researches are needed to confirm these evidences.
Evaluation of thyroid-stimulating hormone-increased, hypertriglyceridemia and proteinuria as markers of anlotinib efficacy in advanced soft tissue sarcoma.
Authors: Chi Yihebali , Yao Yang , Fang Zhiwei , Wang Shusen , Huang Gang , Cai Qiqing , Shang Guanning , Wang Guowen , Qu Guofan , Wu Qiong , Jiang Yu , Song Jianmin , Chen Jing , Zhu Xia , Cai Zhengdong , Bai Chunmei , Lu Yongkui , Yu Zhihua , Shen Jingnan , Cai Jianqiang 
Published: May 2020

e23548 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. The most common adverse events with anlotinib were hypertension (62.66%), thyroid stimulating hormone (TSH) increased (56.33%), hypertriglyceridemia (50%), hand-foot syndrome (48.10%) and proteinuria (36.08%) similar to other vascular endothelial growth factor receptor pathway-targeted therapies. We had evaluated the anlotinib-induced hand-foot syndrome and hypertension with clinical outcome in aSTS patients previously. Here we investigated thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria on clinical outcome in aSTS patients treated with anlotinib. Methods: We conducted a review of patients enrolled in ALTER0203. Median PFS was analyzed in patients with thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria vs patients with no thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria. All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. During the study, TSH increased was observed in 89 patients (56.33%). Hypertriglyceridemia was observed in 79 patients (50%). Proteinuria was observed in 57 patients (36.08%). Median PFS was longer in patients with TSH increased vs patients with no TSH increased (8.40 vs 4.23 months, p = 0.015). Patients with any grade TSH increased while on anlotinib had an adjusted hazard ratio for progression of 0.64 compared to those without TSH increased. Also, median PFS was longer in patients with hypertriglyceridemia and proteinuria vs patients with no hypertriglyceridemia and proteinuria (8.43 vs 4.13 months, p = 0.002; 8.40 vs 4.37, P = 0.048). Patients with any grade hypertriglyceridemia and proteinuria while on anlotinib had an adjusted hazard ratio for progression of 0.59 and 0.75 compared to those without hypertriglyceridemia and proteinuria respectively. Conclusions: In this retrospective analyses, TSH increased, hypertriglyceridemia and proteinuria can serve as biomarkers in aSTS patients treated with anlotinib. Clinical trial information: NCT02449343 .
Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors.
Authors: Nishida Yoshihiro , Urakawa Hiroshi , Nakayama Robert , Ozaki Toshifumi , Ae Keisuke , Matsumoto Yoshihiro , Ando Yuichi , Kuwatsuka Yachiyo , Ueda Takafumi , Kawai Akira 
Published: May 2020

e23569 Background: Malignant peripheral nerve sheath tumor (MPNST) is a malignant soft tissue tumor that does not respond well to chemotherapy and often develops on the basis of neurofibromatosis type 1 (NF1). The purpose of this study was to examine the effects of pazopanib on MPNST. Methods: This study was designed as a physician-initiated phase II clinical trial of pazopanib in patients with MPNST with unresectable or distant metastases. Eleven large hospitals were selected from the Japanese Musculoskeletal Oncology Group (JMOG), and patients were registered between July 2016 and August 2018. The primary endpoint was set to clarify the clinical benefit rate (CBR, including complete or partial response and stable disease) at 12 weeks for pazopanib according to Response Evaluation Criteria in Solid Tumors (RECIST1.1). Progression-free survival and overall survival were set as secondary endpoints along with the safety of this treatment. The clinical benefit rate based on Choi evaluation at week 12 was also set as the secondary endpoint. Results: The study enrolled twelve patients with MPNST. Grade 2 was 7 and grade 3 was 5 by according to the FNCLCC evaluation. Median follow-up period was 10.60 (1.74-22.85) months. Six were male, and six were female. Median age was 49 (20-76). After 12 weeks of pazopanib treatment, CBR was 50.0% (6 of 12 patients) and 50.0% (6 of 12 patients) at RECIST and Choi criteria, respectively. The median progression-free survival was 5.4 months for both RECIST and Choi. Interestingly, the median progression-free survival was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 for both RECIST and Choi. The median overall survival was 10.6 months. The adverse events of Grade 4 was neutropenia in one person and lipase elevation in one person. Grade 3 adverse events observed in ≥10% of patients were increase of AST and ALT, and decrease of white blood cells. Conclusions: The results of this pazopanib clinical trial were comparable to those of previous doxorubicin-based chemotherapy, and better than those of other molecular targeted therapy. Although accumulation of cases is necessary, pazopanib treatment for MPNST might be a safe and promising treatment, particularly for grade 3 MPNST. Clinical trial information: UMIN000019303 .
Current treatment efficacy for metastatic soft tissue sarcoma: A targeted literature review.
Authors: Stirnadel-Farrant Heide , Mahajan Anadi , Dhillon Navdeep , Patel Nashita , Pokras Shibani 
Published: May 2020

e23577 Background: Soft tissue sarcoma (STS) is a rare malignancy with an annual incidence rate of < 5 cases per 100,000 persons; outcomes for metastatic STS (mSTS) are poor. A targeted literature review was conducted to quantify the efficacy/effectiveness of current mSTS therapies. Methods: A structured search based on the population, intervention, comparator, outcome, study type (PICOS) framework was performed on articles (2009–2019) in MEDLINE, Embase, and Cochrane Central. Limited congress searches (ESMO, AACR, ASCO 2016–2018/2019) were also conducted. Clinical trials (CT) and observational studies (Obs) involving patients (pts, any age) with advanced mSTS receiving any pharmacological intervention were included. After screening, selected efficacy (CT) or effectiveness (Obs) endpoints (including progression-free survival [PFS], overall survival [OS], overall response rate, and duration of response) stratified by line of treatment (LOT, if available) were extracted. Results: Overall, 85 studies (56 CT, 29 Obs) met inclusion criteria; study size was 20–4,274 pts. PFS and OS (from 70 studies) were reported for pts with mSTS treated with a wide range of interventions including doxorubicin, trabectedin, pazopanib, and gemcitabine. Across any LOT, median PFS ranged 1.5–9.3 months in CT and 2.1–11.0 months in Obs; ranges were 5.7─28.8 months and 7.0─38.6 months, respectively, for OS. Median PFS and OS were generally lower with later (vs initial) LOT; few studies assessed ≥4 LOT (Table). Outcome data (any LOT) for trabectedin and pazopanib (the only approved targeted mSTS treatments) are shown in Table. Conclusions: This review of the efficacy/effectiveness of current treatments highlights the unmet clinical need for therapies that improve survival outcomes in pts with mSTS. Results may be influenced by small sample size, pt population, and care improvements over the period studied. [Table: see text]
Relationship described by bereaved caregivers (BCGs) between blood transfusions and hospice utilization for loved-ones (LOs) who died from acute myeloid leukemia (AML).
Authors: Cripe Larry Dean , Baker Layla , Sargent Katie , Martin Caroline , Cottingham Ann H. 
Published: May 2020

e24002 Background: Patients with AML may under-utilize hospice due to a reluctance to discontinue potentially life-sustaining transfusions. Transfusions while on hospice are a proposed solution. Methods: Nineteen BCGs completed brief surveys and participated in semi-structured interviews. Interviews were audio-recorded, transcribed and qualitatively analyzed for content related to transfusions and hospice enrollment. Results: Surveys: Four out of 16 BCGs reported their LOs received transfusions until death. The time between last transfusion and death was within 2 weeks (12/19) and more than 1 month (3/19). BCGs reported the purpose of transfusions in the last month of life was to live longer (6) and/or to feel better (10). Interviews: The research team identified 5 points relevant to any connections between transfusions and hospice enrollment: 1. Only 2 of 19 BCGs described a decision to delay hospice enrollment due to inability to continue transfusions while on hospice. Both reported gaining enhanced knowledge about their LOs prognosis and coming to agreement that transfusions were burdensome and not justified. 2. The majority of BCGs described becoming aware that the doctor discontinued transfusions rather than reporting that the discontinuation of transfusions was a decision made by their LO. 3. BCGs described a “logical” and accepted transition from chemotherapy and transfusions to transfusions alone to no transfusions. 4. BCGs’ perspectives on transfusions evolved from transfusions as necessary to may be helpful to no longer indicated. They recall experiencing and accepting this progression rather than discussing the transition with providers. 5. Several impediments to hospice unrelated to transfusions were identified: rapid decline of LO, no perceived need for hospice, equating hospice with a home-based service, and bias against hospice due to past experiences. Conclusions: The desire for ongoing transfusion support is not a major impediment to hospice enrollment in the experience of BCGs. Providing transfusions on hospice may not address the low rates of hospice utilization.
Efficacy of tumor treating fields (TTFields) in elderly patients with newly diagnosed glioblastoma (GBM): Sub-group analysis of the phase III EF-14 trial.
Authors: Ram Zvi , Kim Chae-Yong , Zhu Jay-Jiguang 
Published: May 2020

e24019 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma. In the EF-14 [NCT00916409] phase 3 GBM study, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. The aim of the following post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. Methods: All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse events were compared between the TMZ + TTFields arm and the TMZ alone arm. Results: The median age was 69 (range: 65-83), 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TTFields + TMZ versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P < 0.0236). Median OS was 17.4 months versus 13.7 months in the TTFields + TMZ versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P < 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TTFields + TMZ and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields. SAEs were considered related to TMZ or to the underlying disease. Grades 1-2 skin AEs were observed in 51% of patients. Conclusions: Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ + TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade 3-4 toxicity. Clinical trial information: NCT00916409 .