bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of combined BCL-2/MCL-1 inhibition as a therapeutic approach for synovial sarcoma.
Authors: Fairchild Carter Kent , Floros Konstantinos , Jacob Sheeba , Coon Colin , Puchalapalli Madhavi , Hu Bin , Dozmorov Mikhail , Koblinski Jennifer , Smith Steven , Domson Gregory , Ebi Hiromichi , Faber Anthony , Boikos Sosipatros Alexandros 
Published: May 2020

e23561 Background: While Synovial Sarcoma (SS) only accounts for about 10% of soft tissue sarcomas (STS), or ~10,000 cases/year, ~4,000 of these will be fatal. Little benefit has been seen with newer combination chemotherapies and immune checkpoint inhibitors. SS is a transcription factor-driven cancer characterized by an t(X;18) chromosomal translocation resulting in the SS18-SSX fusion gene. SS is also known to overexpress the anti-apoptotic protein BCL-2, which has been used as a diagnostic marker for SS. Venetoclax, the FDA approved BH3 mimetic which specifically inhibits BCL-2, has been used to treat BCL-2-driven hematological cancers. Yet, preclinical studies of venetoclax, currently in clinical use for BCL-2 related hematologic malignancies, have failed in SS, raising the possibility of other BCL-2 family members playing a role in resistance. Methods: Publicly available gene expression databases of SS were queried for expression of BCL-2 family member expression, including the endogenous MCL-1 inhibitor, NOXA. Six SS cell lines, including ASKA, HS-SY-II, Yamato, SW982, SYO.1, and an ex vivo line from a SS patient-derived xenograft (PDX) were tested in vitro with combinations of venetoclax and the MCL-1 inhibitor S63845, using cell viability assays. In vivo testing employed both a patient-derived xenograft (PDX) model of SS and a cell line derived (SYO.1) xenograft model. Results: Queries of published gene expression data for SS demonstrated that SS expresses low levels of the endogenous MCL-1 inhibitor, NOXA, nominating a mechanism for intrinsic venetoclax resistance in these tumors, and suggesting rational combination of venetoclax and the MCL-1 inhibitor, S63845. In vitro, SS all cell lines possessing the SS18-SSX fusion gene demonstrated synergistic sensitivity to combined S63845 and venetoclax, despite generally insensitivity to either drug as monotherapy. Importantly, in an SS PDX, we demonstrated S63845 and venetoclax synergize to induce tumor regression. In the SYO.1 xenograft model, combination therapy significantly reduced tumor growth compared to no treatment or single agent groups. Conclusions: These findings provide the preclinical rationale for translation of the rational combination of BCL-2 and MCL-1 inhibitors into clinical trials for SS.
Efficacy of anlotinib in advanced soft tissue sarcoma by age, gender, and ECOG performance status.
Authors: Fang Zhiwei , Yao Yang , Cai Jianqiang , Chi Yihebali , Wang Shusen , Huang Gang , Cai Qiqing , Shang Guanning , Wang Guowen , Qu Guofan , Wu Qiong , Jiang Yu , Song Jianmin , Chen Jing , Cai Zhengdong , Zhu Xia , Bai Chunmei , Lu Yongkui , Yu Zhihua , Shen Jingnan 
Published: May 2020

e23562 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. We evaluated the relationship between age, gender and ECOG performance status. Methods: Median PFS was analyzed in subgroups of age (≤40 y; > 40 y), gender (male; female) and ECOG performance status score (0; 1). All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. 79 patients (50.0%) were > 40 y. Median PFS was longer in patients of age > 40 y than ≤40 y (7.43 vs 5.43 months, P = 0.40). In patients receiving anlotinib, 76 patients (48.1%) were female and median PFS was longer in female than male (9.80 vs 4.43 months, P = 0.002). All enrolled patients had a Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 107 patients (67.7%) were with poor PS (ECOG PS = 1). The median PFS was longer in PS of 1(8.43 vs 4.73, P = 0.53) than PS of 0. Conclusions: In patients receiving anlotinib, longer mPFS was observed in patients of age > 40 y, ECOG PS = 1 and female. Clinical trial information: NCT02449343 .
Retrospective analysis of intraoperative radiation therapy with low-kilovoltage x-rays (IORT-LK) in soft tissue sarcomas (STS).
Authors: David Waldec Jorge , Hanriot Rodrigo De Morais , Di Paula Filho Raphael Paulo , Amaral Silva Pedro Alexandre Ismael , Costa Marcos Andre De Sa Barreto , Yen Cheng Tzu , de Mello Evandro Sobroza 
Published: May 2020

e23575 Background: STS include a heterogeneous group of malignancies that arises from or into connective tissues and limbs are the preferential primary sites. An adequate local control with multimodality therapy can be obtained in most cases. An additional approach, that is, the IORT-LK is able to deliver high dose to risky areas for recurrence, minimizing the toxicity to structures around the target. Such an importance is even greater in abdominal sarcomas, because there is some difficulty in removing the whole neoplasia with clear margins. IORT-LK has the advantage of higher Relative Biological Effectiveness (RBE), a mathematical model that measures the potential for tumour double-strand break (radiation effectiveness), that is close to Proton beam and higher than electron beam. Nevertheless, IORT-LK is not free of complications. It has been reported peripheral neuropathy and enteritis, in cases of limb and abdominal STS, respectively. Methods: In this retrospective study from a single Brazilian institution (Hospital Alemão Oswaldo Cruz), we reported 6 patients with histologically confirmed STS, that underwent IORT-LK (Intrabeam - Carl Zeiss). There are 3 male and 3 female patients, with a median age 48 years, and mean of 39 years. The histological subtypes are as follows: fibromyxoid sarcoma, high grade pleomorphic sarcoma, desmoid tumor, chondrosarcoma, dedifferentiated liposarcoma and malignant schwannoma - one subtype for each patient. The primary sites are: inferior limb (3), superior limb (1) and abdomen (2). Results: IORT-LK was administered in doses that ranged from 14 to 15 Gy to the involved area. Two patients, each one with a limb STS, received also neoadjuvant chemotherapy. With a mean follow-up of 30 months, there is no local recurrence among the 6 patients reported. The first patient received the IORT-LK in April, 2017 and the last one in July, 2019. All of them had clinical observation up-to-dated on January, 2020. No serious complications were observed, but one patient had a moderate local infection. Conclusions: The therapy was well tolerated. We must emphasize that dose previously used by Brussiers was slightly superior than ours but with electrons and not Low-Kylovoltage. In his pilot study it was used 17 Gy for treatment of abdominal sarcomas. In sum, we believe that IORT-LK has higher RBE than previous available equipment and can improve local control of STS, mainly those that arise on the extremities. Future studies must be carried out to confirm our initial impression.
Searching for the “exit ramp”: Bereaved caregivers (BCGs) describe discontinuation of transfusions at the end of life (EOL) for loved-ones (LOs) dying from acute myeloid leukemia (AML).
Authors: Cripe Larry Dean , Martin Caroline , Sargent Katie , Baker Layla , Cottingham Ann H. 
Published: May 2020

e24000 Background: Transfusions may delay hospice care. This study examined how transfusions and other factors influenced care transitions, including decisions related to hospice care, for patients with AML from diagnosis to death. Methods: Nineteen BCGs participated in semi-structured interviews about their experiences. Interviews were audio recorded, transcribed and qualitatively analyzed. Results: The research team identified three stages in BCG experience: 1. Acceptance and Hope: BCG initial response to an AML diagnosis was acceptance of chemotherapy and transfusions as necessary to extend life and potentially cure the AML. Benefits of treatment were emphasized over potential harms or details. 2. Reading the Signals: BCGs learned to interpret information from a variety of sources to appreciate whether their LO was heading in the right direction or not. The signals included discussions with or decisions of the oncologist, changes or no changes in lab results, changes in the LO’s physical condition, and changes in care location in the hospital (e.g., ward bed to ICU bed). Signals were either cautionary or hard stops. Cautionary were seen as conditional, e.g., if things did not improve then LO may be at EOL. Cautionary signals were described as vague and ambiguous. Hard stops were clearer and were typically a clinician decision or recommendation to discontinue treatment and/or transfusions because there was no longer a possibility of benefit. 3. Searching for the Exit-Ramp: Hard stops precipitated awareness that death was imminent and an often-rushed search for how to care for the LO at the EOL. In retrospect the transition made sense to the BCG but they often felt unprepared at the time of transition. Conclusions: The benefits and burdens of transfusions are important signals to BCG about the EOL. Early cautionary signals and discussion may prepare BCG for transitions. Continuation of transfusions in hospice may eliminate a chance for critical conversations.
Systematic analysis of extracting data on advance directives from patient electronic health records in terminal oncology patients.
Authors: Skelton William Paul , Starr Jason Scott , Rahmanian Kiarash , Guenther Robert , Allen William L. , George Thomas J. , Moseley Ray E. 
Published: May 2020

e24011 Background: Advanced care planning and living wills are critical components of caring for patients at the end of their lives. Advance directives are designed to be implemented when a patient meets the legal definition of terminal and is deemed incapacitated. By reviewing the electronic health record (EHR) in patients with terminal cancer, we sought to evaluate whether advance directives were appropriately implemented. Methods: A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database, and data analysis was completed using SAS. Results: Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was “progressive” (36.6%) and “palliative” (31%). The most common clinical terminology indicating incapacity was “altered mental status” (25.6%), and “not oriented” (14%). 34 patients (6.8%) met all criteria of having a terminal diagnosis, a documented AD, and deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided to these patients. Conclusions: End-of-life care is a challenging albeit vital part of the practice of medicine. This study provided insight on to how ADs are managed in day to day practice in a hospital. From our analysis, it is clear that physicians are able to identify when a patient is terminal; however, it is typically later than it should have been recognized (and thereby, leading to delays in the implementation of the patient’s AD). Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.
Sarcopenia and clinical evaluation in predicting treatment tolerability and outcomes in aggressive non-Hodgkin B cell lymphoma.
Authors: Drory Samuel Bernard , Forget Marie-France , Wang Han Ting , Fleury Isabelle , Ahmad Imran , Marchand Laurence 
Published: May 2020

e24018 Background: Sarcopenia is associated with decreased treatment tolerance and overall survival in aggressive large B-cell lymphoma, the most common non-Hodgkin lymphoma (NHL) in the geriatric population. The impact of sarcopenia on event-free survival (EFS) in older adults with an aggressive B-cell NHL remains unclear. Our primary endpoint was to evaluate the association between sarcopenia and 6-month EFS in adults aged 65 and older diagnosed with an aggressive B-cell NHL. Methods: We performed a retrospective cohort study of adults 65 years or older diagnosed with an aggressive B-cell NHL between July 1st 2014 and June 30th 2018 who completed 1st line chemotherapy in an academic center. Sarcopenia was defined as the lowest tertile of psoas muscle index (PMI). Psoas muscle area was measured on a single axial slice at L4 using CoreSlicer software, and divided by height squared. EFS defined as no death, relapse or hospitalisation, was compared between sarcopenic and non-sarcopenic individuals using Kaplan-Meier curves and multivariable Cox regression. Results: In our cohort of 62 older adults, median age was 74 (interquartile range (IQR): 69-78) and median PMI was 7.2 cm2/m2 (IQR: 5.9-8.4). Twenty patients were sarcopenic with a median PMI of 5.5 (4.8-6.3) cm2/m2. Most patients (56%) received full dose chemotherapy. Among patients who received an attenuated dose of chemotherapy, the percentage of patients with sarcopenia was similar to the one of patients receiving full dose chemotherapy (39% vs 24%, p=0.200). After controlling for age, sex, ECOG, cardiac disease, creatinine, LDH and hemoglobin levels, sarcopenia was associated with a lower EFS (HR 3.5, 95%CI: 1.1-11, p=0.032). Although sarcopenia was not associated with the choice of an attenuated chemotherapy intensity, when stratifying for chemotherapy intensity, there was a trend in favor of decreased EFS with sarcopenia in the full dose group (p=0.095), which did not reach statistical significance. Conclusions: Sarcopenia is associated with a lower 6-month EFS in older adults who completed first line chemotherapy. These individuals may benefit from pre-chemotherapy geriatric evaluation and tighter follow-up.
The impact of frailty on the occurrence of immune-related adverse events in older patients with advanced melanoma.
Authors: Bruijnen Cheryl P. , Koldenhof Josephine J , Tonk Erwin H.J. , Verheijden Rik Jasper , van den Bos Frederiek , Emmelot- Vonk Mariëlle H. , Witteveen Petronella , Suijkerbuijk Karijn 
Published: May 2020

e24028 Background: Immune checkpoint inhibitors (ICIs) have changed the melanoma treatment landscape by inducing durable responses and significantly improving survival. ICI can cause immune-related adverse events (irAES) ranging from mild to life threatening. Clinical trials have not shown major increase of irAES in older patients when compared to younger patients. However, older patients have been underrepresented and were relatively fit in these trials. In this study, we assessed the occurrence of irAEs treated with systemic corticosteroids and/or leading to treatment discontinuation (relevant irAEs) in older patients with melanoma and, if relevant irAEs occurred more often in frail patients, as assessed with the Geriatric 8 (G8). Methods: Patients ≥70 years diagnosed with advanced melanoma, about to start with ICI, and screened with a G8, were enrolled in this prospective observational study. Patients were classified according to the G8 score as “fit” (G8 score >14) or “frail” (G8 score ≤14). Toxicity was scored according to CTCAE v4.03. Primary outcome was occurrence of relevant irAEs in “fit” and “frail” patients. Secondary outcomes were the occurrence of irAEs any grade and severe irAE (grade ≥3). Results: In total, 49 patients were included for statistical analyses. Thirty-three patients were classified fit according to the G8 and, 16 patients were frail. Relevant irAEs occurred statically significantly more often in in frail patients: 12 (75%) versus 15 patients (46%) ( p=0.05). In addition, more irAEs grade ≥3 were reported in frail patients, although not significant: 7 (44%) versus 8 patients (25%) ( p= 0.11). Conclusions: Frailty, classified by the G8, is associated with the occurrence of relevant irAEs in the older patient with advanced melanoma. These data need to be confirmed in larger series.
Patient self-management and health maintenance at lung cancer diagnosis and during treatment.
Authors: Feliciano Josephine Louella , Trosman Julia Rachel , Weldon Christine B. 
Published: May 2020

e24036 Background: Health maintenance is an integral part of lung cancer care starting at diagnosis and throughout cancer care continuum. Patient self-management (pSM) is a key strategy thought to contribute to promotion of health maintenance in cancer patients (McCorkle, CA Cancer J Clin. 2011, NAM 2014), but its role in lung cancer has been unexplored. We conducted this study as baseline before conducting a quality improvement (QI) to optimize health maintenance utilization and patient self-management in lung cancer. The Q will implement the 4R model (Right Info / Care / Patient / Time) for care delivery, patient self-management and teamwork (Trosman, JOP 2016). Methods: We surveyed patients with lung cancer stages I-IV undergoing cancer treatment at a tertiary cancer center 2018-2019, assessing pSM and health maintenance utilization by patients. We used simple frequencies and Fisher’s exact test in analyses. Results: Survey response rate: 81%, 149/185. We found gaps of at least 20% in all 6 assessed pSM metrics: “know stage of your cancer” (78%), “ability to explain your care to others” (73%), “clarity of care plan” (72%), “ability to manage your own care” (71%), “seldom overwhelmed, not in control of your care” (65%), and “clarity of timing and sequence of care” (35%). High level of composite pSM score ( > 2.8 on 0-4 scale) was found for 50% of patients. Patients also reported insufficient utilization of health maintenance along the 7 metrics we assessed (Table). The level of pSM impacted receipt of health maintenance: patients with high composite pSM score were significantly more likely to obtain 4 of the 7 health maintenance metrics than patients with lower composite pSM score (Table). Conclusions: While serious gaps exist in health maintenance utilization in lung cancer, it is significantly associated with the level of patient self-management. Strategies to improve patient self-management should be utilized to promote health maintenance during lung cancer treatment. Our program to implement the 4R model of cancer care delivery will evaluate if and how 4R facilitates these improvements. [Table: see text]
The prevalence and sociodemographic predictors of mobile health applications ownership among cancer survivors.
Authors: Dosunmu Gideon T , Hagan Kobina Kwantsin , Udoye Chike , Khushman Moh'd M. 
Published: May 2020

e24046 Background: The transition of cancer patients from patients to survivors is challenging. Cancer survivors often experience chronic physical, social and mental health needs which remain largely unmet. Due to the growing population of cancer survivors and limited resources available to address their needs, mobile health applications (apps) have emerged to help cancer patients in assuming their new role as survivors. Here, we explored the prevalence and sociodemographic predictors of mobile health apps ownership among Cancer Survivors in the United States using a nationally representative sample. Methods: Data from cycles 1 (2017) and 2 (2018) of the 5th edition of the Health Information National Trends Survey (HINTS 5) was reviewed. Descriptive statistics was used to evaluate the sociodemographic characteristics and the prevalence of mobile health apps ownership among cancer survivors. Univariate logistic regression models were used to explore the relationship between sociodemographic predictors and mobile health apps ownership. Results: We identified 1,097 (weighted estimate of 44,666,781) individuals who self-reported having been diagnosed with cancer in the . Of these, 57.39% were females, 79% were whites, 47.18% had 2 or more medical comorbidities, 63.7% were unemployed and about 50% were aged 65 or more. Prevalence of mobile health apps ownership was 44.82%. Among all the sociodemographic variables; educational level (p = 0.015), income (p = 0.014) and employment status (p < 0.005) were predictors of mobile health apps ownership among cancer. Conclusions: Cancer survivors are digitally connected and can be approached through mobile health apps. In our study, the prevalence of mobile health apps ownership in cancer survivors was 44.8%. Educational level, income and employment status were identified as predictors of mobile health apps ownership. Due to the growing population of cancer survivors and limited resources available to address their needs, efforts to address barriers of mobile health apps adoption and utilization should be encouraged.
Khorana score as a predictive tool of venous thromboembolism in cancer patients in rural practice.
Authors: Khalil Ahmed , Ortolano Daniel , Simunich Thomas , Saad Eldin Mohamed , Hussain Munawwar , Higbee Sheetal L. 
Published: May 2020

e24049 Background: The Centers for Disease Control and Prevention (CDC) estimates that 60,000 to 100,000 Americans die from venous thromboembolism (VTE) annually, costing the U.S. healthcare system $7–10 billion each year. VTE is a leading cause of mortality in cancer patients, and risk is particularly elevated in rural areas, where cancer death rates are higher than in metropolitan areas. The Khorana score has been shown to predict VTE incidence before starting treatment and as such identify those patients that would benefit most from VTE prophylaxis. We aimed to replicate the utility of the Khorana score on a rural population of cancer patients to help address VTE in advance. Methods: From our electronic health records system, we extracted data from cancer patients (age ≥ 18 years) who had begun chemotherapy from 2017-January through 2019-August. Patients who were pregnant, had undergone hormonal therapy or major surgeries within three months prior to VTE diagnosis, or had a history of coagulation disorders or VTE prior to starting chemotherapy were excluded. A Khorana score (0—6, interval = 1) was calculated for each prior to their starting chemotherapy and was used for VTE risk stratification, 0 – low; 1,2 – intermediate; ≥3 – high. We hypothesized that VTE occurrence during the first 6 months following the start of treatment would be positively associated with risk category. Results: The 144, mostly female (64%), cancer patients meeting inclusion had a mean age of 75 years (range 48—95) and VTE risk stratification: 10% (15) high, 67% (96) intermediate, and 23% (33) low. In the first 6 months of starting treatment, 6% (9/144) developed VTE, with a prevalence of 20% (3/15) amongst patients stratified as high risk, 5% (5/96) of intermediate, and 3% (1/33) of the low risk group. A linear-by-linear association of the observed Khorana scores with VTE occurrence implies a meaningful positive association between VTE risk stratification by Khorana score and VTE, chi-square (1,144) = 4.018, p = .045. Conclusions: The trend of higher VTE prevalence in intermediate and high risk patients supports the observed positive association between Khorana score VTE risk category and a greater percentage of patients experiencing VTEs with increasing risk. This trend may likely be amplified with application to a larger number of patients. The study limitations include the lack of diversity of organ affection and sample size, specifically upon risk stratification. However, initiating a discussion about the risks and benefits of VTE prophylaxis prior to starting treatment is of outmost importance.