bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of implementing a resident oncology video curriculum.
Authors: Brondfield Sam , Iverson Nicholas , Subbaraj Lakshmi , Babik Jennifer
Published: March 2020

10500

Background: ACGME survey results consistently show that 40% of University of California, San Francisco (UCSF) internal medicine (IM) residents are dissatisfied with their oncology education—higher than the oncology national average and highest among UCSF IM subspecialties. A needs assessment revealed that UCSF residents desire online oncology resources for asynchronous learning. To address this need, we sought online oncology videos targeted to residents but found none. We thus used cognitive theory of multimedia learning principles to develop an oncology video curriculum and evaluated three feasibility components: demand (frequency of use), efficacy, and acceptability. Methods: We chose common cancers from the ABIM blueprint and filmed five 10-minute videos of UCSF oncologists discussing content they chose for residents. We created modules with pre/post tests derived from video content. After a pilot, we sent links to all IM residents on required oncology clinic rotations over four months (n = 25) and offered protected clinic time for optional completion. We compared pre/post test scores with a paired t test and surveyed residents. Results: Demand: 72% (18 of 25) completed ≥1 module; 32% completed all 5. Efficacy: The mean pre- vs. post-test score improved (50% vs. 87%, p = 0.002). Acceptability: 64% completed the survey. Of those who completed ≥1 module, 93% (13 of 14) felt strongly that the videos contributed to their knowledge. 93% recommended the videos to others. Residents praised the length, key points, and pre/post tests. Finding time for the modules was difficult; most did them at home. Suggestions included focusing on fundamentals and creating videos for all common cancers. Conclusions: We present demand, efficacy, and acceptability evidence supporting the feasibility of a resident oncology video curriculum. Formal protected time for module use is critical. We will focus on fundamentals for generalists as we make more videos. We will track ACGME survey results, examination scores, and clinical performance to study impact. We aim to publish the modules online for broader use and as a model solution to address similar needs across specialties and institutions, as complex resident schedules increasingly require asynchronous learning.
Which factors are influencing good digital education? Analysis on ecancer programs from major international congresses.
Authors: Burke Danny , Thalmann Eva , McVie Gordon
Published: March 2020

10501

Background: Factors limit the opportunities for healthcare professionals to attendinternational conferences including lack of financial support or time. Digital education from Independent Medical Education providers is therefore an important source of education for clinicians. One such provider is the ecancer Global Foundation (ecancer), an educational charity who publish ecancer.org. A landmark ecancer activity is sharing developments from conferences with video interviews of experts discussing the key data. Methods: We aim to get a deeper understanding of the factors that influence viewer satisfaction with these resources including whether industry support (through un-restricted educational grants) had a significant impact. Viewer satisfaction is measured using 3 metrics: 1. Viewer feedback; 2. Number of views; 3. Average viewing time. The analysis is based on programs from ASCO GU 2018, ASCO 2018 andESMO 2018 covering prostate and lung cancer education including unsupported as well as industry supported programs by Janssen, and two other pharma companies through unrestricted educational grants. Results: 68 videos were analysed with 95,249 views. This included 4 Expert to Expert Interviews, 4 Expert Panel Discussions and 60 To Camera Interviews. Of the 68 videos, 24 were supported by industry and all were peer-reviewed. Viewer feedback includes Net Promotor Score and a measure of likely impact on clinical practice as a result of watching the video. Conclusions: Expert to Expert and Expert Panel formats achieve higher viewer satisfaction than To Camera Interviews. Viewer satisfaction scores are very similar for industry supported vs non-industry supported content. These findings seem to suggest that the format of the educational video is a more important factor than whether it is supported by industry when impacting viewer satisfaction.[Table: see text]
Development of an “Art of Oncology” curriculum to mitigate burnout and foster solidarity among hematology/oncology fellows.
Authors: Richardson Daniel R. , Winzelberg Gary , Rosenstein Donald Lee , Collichio Frances A.
Published: March 2020

10507

Background: Oncologists and fellows in Hematology/Oncology (HO) training programs report high levels of burnout. The ACGME requires accredited programs to have a mechanism to foster “well-being” and “ethical behavior” among fellows. A loss of solidarity among oncology professionals may contribute to known causes of burnout, such as heavy workload and severity of patient illness, that may in turn negatively impact patient outcomes. Methods: Through a multidisciplinary process involving fellows and faculty from psychiatry, palliative care, and hematology/oncology, a 3-year longitudinal “Art of Oncology” (AOO) curriculum was created for HO fellows at our institution to foster solidarity and mitigate burnout. The curriculum principally involved monthly hour-long sessions intended to promote reflection on oncologists’ shared experiences and the humanistic aspects of caring for patients with cancer. Facilitated by topic experts utilizing personal and published narratives, sessions foster group discussion. Fellows are also invited to write a personal narrative reflecting on their role as an oncologist. Topics include death and dying, caring for patients after treatment failure, cultivating resilience, religion/spirituality, the moral responsibility of oncologists, and oncology as a calling. Cancer patients and spouses were invited to facilitate a session to emphasize the patient experience. Burnout and preparedness for covered topic areas were measured prior to curriculum initiation and will be re-assessed annually. Results: The curriculum began in 2018. Of current fellows, 94.7% (18/19) completed the initial survey. A greater proportion of HO fellows participated in the AOO sessions than non-AOO didactic lectures (mean attendance, 59.2% v. 42.7%, p = 0.037). At curriculum initiation, most fellows reported burnout a few times or more a month (all fellows = 75%, 1st year = 85.7%, 2nd year = 80%, and higher = 62.5%). Conclusions: The implementation of a dedicated curriculum to foster solidarity among HO fellows through narrative medicine and group discussion of the humanistic aspects of oncology is feasible. A substantial degree of burnout exists among HO fellows, even incoming fellows. Further research to assess whether this curriculum mitigates burnout is needed. Because burnout is already a problem for incoming fellows, further work should investigate interventions aimed at ameliorating burnout among both residents and fellows.
ASCO Direct GU: A multistakeholder blended-learning project to make global education local.
Authors: Miller Kurt , Malhotra Suneil Singh , Nanchanatt Daina , Thalmann Eva , Van Der Zwart Robert A. , Joniau Steven
Published: March 2020

10515

Background: International clinicians (HCPs) often find it difficult to attend North American congresses due to time out of the clinic, institutional travel restrictions, & individual financial burden. HCPs continue to highlight the value of peer to peer scientific exchange at international meetings & peer reviewed journals. Coupled with the dramatic increase of new scientific & clinical data that are rapidly changing clinical paradigms, there is a need for an effective & efficient digital solution to reach as many HCPs as possible. ASCO GU Direct sought to develop an educational program that culled the latest clinical & scientific data from ASCO GU in real time to global HCPs. ASCO GU Direct is a partnership between ASCO, MEDtalks Netherlands, Bayer & Janssen to drive global education locally since 2016. The live connection was broadcast in real time to local digital hubs in Europe, Middle East & Asia, where an expert panel from ASCO GU reviewed key scientific data with local HCPs in real time. HCPs were able to view ASCO presentations & ask questions to the panel despite time zone & geography. Methods: We present results from the surveys done with participating HCPs to understand the effectiveness of this blended program by examining the quality & objectivity of the content, impact on their clinical treatment, & the Net Promotor Score (NPS). Results: To measure quality & objectivity, NPS was calculated based on HCP responses to: “Would you recommend ASCO GU Direct to a colleague.” The NPS was 59 in 17 & 72 in 18 (scale: -100 to +100), showing willingness to recommend the educational program. Conclusions: Providing digital access can effectively & efficiently bridge gaps that would otherwise exist for international HCPs who did not attend ASCO GU. Digital access through this collaboration with live access to experts provides an excellent solution for HCPs who want to remain updated on clinical & scientific data.
Cross-cultural validation of a medical leadership competencies survey in Latin-American physicians: A multinational study.
Authors: Mano Max S. , Gomes Rafaela , Barrios Carlos H. , Marta Gustavo Nader , Villarreal-Garza Cynthia , Frasson Antonio Luiz , Sternberg Cinthya , Clara Renan , Simon Sergio D. , Werutsky Gustavo , Çitaku Fadil
Published: March 2020

10517

Background: Despite the growing complexity in the healthcare sector, physicians rarely receive formal training in leadership skills. In a previous survey, Citaku et el identified a set of leadership competencies (LC) which were evaluated by North-American (NA) and European (EU) leaders involved with medical education. We aim 1) To apply this same survey to a population of Latin-American (LA) physicians from the oncology community and related areas who hold leadership positions of various levels; 2) To compare the results with those of the previous survey and 3) To perform subgroup analyses within the LA cohort. Methods: The survey was sent to close to 8.000 members of contributing medical societies from LA countries. In addition to the 63 questions with 5 possible responses, we also collected data on type of institution (private vs public), country of practice, main specialty, gender, age, years of experience in oncology and years of experience in leadership position. Results: We collected a total of 217 responses on a web-based tool. LA leaders placed the highest value on task-management competencies(91,37% of `important` or `very important` responses vs 87,0% for NA/EU; p < .0001), followed by self-management(87,45% vs 87,55%; p = NS), social responsibility(86,83% vs 87,48% ; p = NS), innovation(86,69% vs 85,31% ; p = NS) and leading others(83,31% vs 84,71% ; p = NS). Social responsibility, which was first in importance in the NA/EU survey, was only third in the LA survey. Subgroup analyses revealed significant interactions which will be fully presented. Conclusions: We successfully applied the survey to a population of LA medical leaders from the oncology community and related areas. LC valued by LA leaders somewhat differ from those valued by their NA/EU counterparts, implying that cultural aspects might influence the perception of desired/required LC. We also detected significant variations in the responses within the LA population. Our data might indicate that current physician leadership training programs should be tailored to suit specific needs and cultural aspects of each region. Further validation of this survey in other clusters of world culture is warranted.
Support structures for female physicians: Motivations and barriers to gender-specific conferences and symposia.
Authors: Jain Shikha , Graff Stephanie L. , Swaroop M , Woitowich Nicole C.
Published: March 2020

10518

Background: While nearly half of all medical school graduates are female, women remain underrepresented in the physician workforce. Conferences or symposia designed to address issues relevant to female physicians, such as gender-bias, sexual harassment, and work-life balance are one strategy to improve retention and advancement, yet, limited data exists surrounding their utility. To address this gap, we surveyed a multi-disciplinary group of female physicians to identify motivations or barriers to attendance. Methods: An online survey instrument was distributed nationally via social media and shared by respondents. The survey assessed participants ’ demographics, attendance at gender-specific conferences or symposia, motivations or barriers to attendance, and perceived benefits of attendance. Results: Of 792 respondents, 34% had attended a conference or symposia for women in medicine, while 66% had not. Attendees were significantly more likely to hold a leadership position (68% vs. 43%, p < 0.0001), an academic faculty position (74% vs. 56%, p < 0.0001), and have received a professional accolade within the past year (42% vs. 28%, p < 0.0001). Non-attendees were significantly more likely to be the primary caregiver for children or seniors (64% vs. 56%, p = 0.042). Respondents indicated that an interest in discussion topics, a sense of community, and growth of professional network were key motivators in attendance. The majority of respondents indicated that attendance improved their self-advocacy, self-image, and leadership skills. Of those who did not attend, 51% were unaware of such conferences or symposia. Those who were aware, but unable to attend, cited lack of time as the major barrier to participation. Conclusions: The results of this study provide preliminary data surrounding gender-specific conferences or symposia for women in medicine and highlight opportunities for increased engagement. While not causative, attendees share attributes of professional success and report personal and professional benefits. Lack of awareness and access to child/family care are likely major barriers to participation, which can be addressed through strategic initiatives.
It starts at the top: An analysis of female representation in academic medical oncology (MO), radiation oncology (RO), and surgical oncology (SO) program leadership positions.
Authors: Chowdhary Mudit , Chowdhary Akansha , Patel Kirtesh R. , Royce Trevor J. , Sen Neilayan , Barry Parul Nafees , Jain Shikha , Rao Ruta D. , Levy Mia Alyce , Knoll Miriam , Vapiwala Neha , Wang Dian , Pro Barbara , Marwaha Gaurav
Published: March 2020

10520

Background: Female underrepresentation in academic medicine leadership is well-documented; however, oncology specific data are scarce. This study evaluates female leadership representation in academic medical oncology (MO), radiation oncology (RO) and surgical oncology (SO) programs. Furthermore, we examine the impact of female leadership on overall female faculty representation. Methods: A total of 264 (96%) Accreditation Council for Graduate Medical Education actively accredited MO [144 of 153], RO [93 of 94] and SO [27 of 27] training programs were included. The gender of overall faculty and those in leadership positions (program director and departmental chair/division chief) of each program was determined using hospital websites from 10/01/18 to 01/27/19. The chi-squared goodness-of-fit test was used to examine whether the observed proportion of females in leadership positions deviates significantly from the expected proportion based on the actual proportion of overall female faculty in MO, RO and SO. Two-sample t-tests were used to compare rates of female faculty representation across each program based on the presence/absence of female in a leadership position for MO, RO and SO. Results: Female faculty representation in MO, RO and SO was 37.1% (1,554/4,191), 30.7% (389/1,269) and 38.8% (212/546), respectively. Female representation in leadership positions was 31.5% (82/260), 17.4% (31/178) and 11.1% (5/45), respectively. The observed proportion of females in leadership positions was significantly lower than the expected proportion of females in leadership positions for RO (17.4% vs. 30.7%, p = .0001) and SO (11.1% vs. 38.8%, p = .0001), and demonstrated a trend towards significance for MO (31.5% vs. 37.1%, p = .063). 47.9%, 33% and 18.5% of MO, RO and SO programs had ≥1 female in a leadership position, respectively. Programs that had a female in a leadership position had a higher mean percentage of overall female faculty than those that did not: 41.0% vs 35.0% (p = .0006), 36.0% vs 26.0% (p = .0002) and 39.0% vs 32.0% (p = .348) for MO, RO and SO, respectively. Conclusions: Gender disparity exists in academic MO, RO and SO faculty and is magnified at the leadership level. Programs with a female physician in a leadership position are associated with a higher percentage of female faculty.
From presentation to paper: Gender disparities in oncological research.
Authors: Dijksterhuis Willemieke P.M. , Stroes Charlotte I. , Tan Wan Ling , Ithimakin Suthinee , Calles Antonio , Barriuso Jorge , Oosting Sjoukje , Kolarevic Daniela , Furness Andrew J.S. , Bozovic Ivana , Gomez-Roca Carlos Alberto , Van Laarhoven Hanneke W.M.
Published: March 2020

10523

Background: Gender discrepancies have been identified in authorships of scientific publications, grant applications, and peer review in many disciplines, including oncology. The exact share of women presenting results of oncological studies at large conferences is unknown, while the oral presentation of a study at such a podium enhances the international visibility and recognition of the presenting person. Therefore, we aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Methods: We collected consecutive abstracts presented at the plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and presidential sessions of the European Society for Medical Oncology (ESMO) Congresses. Sex of the presenters and abstract authors, study results (positive vs. negative), and subsequently published papers were identified. Chi square tests were used to compare the distribution of sex over time. The association between presenter’s or last author’s sex and study outcome and impact factors were analyzed using Chi square tests and Mann-Whitney U tests, respectively. Results: Of available abstracts presented at ASCO between 2011 and 2018 (N = 34), and ESMO between 2008 and 2018 (N = 132), presenters were female in 24% and 21%, respectively. Female last authors were seen in 21% and 20% of these ASCO and ESMO abstracts. Of all contributing authors to these ASCO (N = 569) and ESMO (N = 1851) abstracts, 31% and 27% were female, respectively. The distribution of male and female ASCO and ESMO presenters (P = 0.580, P = 0.707, respectively) and abstract authors (P = 0.429, P = 0.062) was similar over the years. Of all abstracts, sex of the presenter or last abstract author were not associated with study outcomes (P = 0.718, P = 0.4331), nor with impact factor of subsequently published papers (P = 0.209, P = 0.661). Conclusions: There is a clear gender disparity in the presentation of oncological research at two main conferences, with less than a third of abstract authors female and less than a quarter of these studies presented by a woman. The lack of visibility of female researchers at presentations on these conferences could impair the acknowledgement for their research, opportunities in their academic career, and even hamper heterogeneity and outcomes in research.
Satisfaction of general versus specialized continuity clinic in hematology oncology fellowship training: A survey.
Authors: Ilyas Sama Imran , Murphy Martina Cathryn , Duff Jennifer Michelle , Close Julia Lee
Published: March 2020

10529

Background: At the University of Florida (UF), oncology fellows participate in two general types of continuity clinic as part of their training. One clinic at the Veterans Hospital (VA) allows them to care for patients in a general clinic setting that encompasses a variety of hematology oncology diagnoses. The other clinic, located at the university site, is disease or system specific (such as breast or GI clinic). Considerable research supports the value of continuity clinic in residency and fellowship training, but the differences in having a general versus specialized clinic for oncology fellows have not been explored. The purpose of this study is to investigate the perceived differences of general versus specialized continuity clinics by recent oncology graduates from UF, and what features of a continuity clinic they feel were most important for an effective and meaningful experience. Methods: An anonymous survey was sent to the last six graduating classes of oncology fellows at UF. The survey contained short demographic questions, followed by five open ended questions pertaining to both continuity clinic experiences. Graduates were asked about their opinions of both the general and specialized clinics during their training at UF. Survey responses were reviewed and coded for common themes. Results: The most common themes that emerged from the surveys were concerning autonomy, supervision, and the diversity of cases and patient population. A majority of respondents felt they had more autonomy and personal responsibility at the VA general clinic, but less direct supervision than at the specialized clinics. They also believed they got a broader exposure of different disease types at the VA general clinic. Surveyed participants also commented on the quality of educational seminars and activities, preceptor expertise and teaching, and ability to observe cutting edge practice and clinical trials. Eleven out of thirty surveys were returned and we anticipate a greater than 50% response for the final poster. Conclusions: Graduated oncology fellows from UF believe that there is a balance that exists between having autonomy and ownership of their patients versus having adequate supervision. Many believe that having “controlled autonomy” and “as much independence as is safe for patients” is key to a meaningful continuity clinic experience during oncology fellowship training.
A novel qualitative methodology study to characterize discrimination and inclusion among hematology/oncology trainees.
Authors: Warsame Rahma M. , Asiedu Gladys , Kumbamu Ashok , Hayes Sharonne , Thompson Carrie A. , Hobday Timothy J. , Price Katharine Andress Rowe
Published: March 2020

10530

Background: Learner wellbeing may be adversely affected by the experience of discrimination. Eliciting details from this vulnerable population about these experiences is a challenge. This study characterizes trainee experiences of discrimination and inclusion to inform graduate medical education (GME) policies and practice. Methods: Anonymous semi-structured, private phone interviews were conducted with fellows after informed consent. No identifying information was exchanged and the interviewer had no supervisory role over learners. Demographic information was obtained via anonymous online survey. Results: Of 29 fellows approached, 20 consented; 17 interviewed (10 men; median age 32 years). Racial & ethnic distribution: 6 Asian, 2 Black, 2 Multi-racial, 4 White, 3 Hispanic/Latino. All fellows reported discriminatory behavior that they either experienced or witnessed. Incidents of discriminatory behavior towards trainees were more common from patients (pts) (n = 41) than staff (n = 12). Discrimination from pts included requesting a different physician based on accent (n = 13), race (n = 11), perceived avoidance of a trainee considered “different” (n = 11), sex (n = 5), & ethnicity (n = 4). Six trainees were aware of policies against pt discrimination but only 1 trainee reported an incident. Trainees did not report because of the nature of incidents (micro aggressions that are difficult to characterize) and sense of futility of reporting. Discriminatory behavior from staff was based on perceived micro aggressions (n = 4), sex (n = 3), ethnicity (n = 3), ageism (n = 1), and sexual orientation (n = 1). Impact on trainees ranged from negative (personal anguish) to positive (motivation to improve communication). Coping mechanisms included debriefing with family/trainees and focusing on good pt experiences. Trainees felt that having diverse co-fellows, involvement on committees, and supportive program leadership promoted inclusivity. Conclusions: Our study found that discriminatory behavior towards trainees is common. Our methodology allows for honest & safe discussions. GME programs must assess their learning climate with respect to bias/inclusivity & develop appropriate processes.
FitFirms: A wellness option for oncology trainees.
Authors: Pathak Bhavana , Eapen Ann M. , Zell Jason A.
Published: March 2020

10537

Background: Burnout in oncologists has been rising over the past decade. Burnout leads to poor patient outcomes and poor physician health. Younger oncologists are at higher risk for burnout. The Firm System was designed by Victor McKusick at the Johns Hopkins hospital in 1975 to integrate faculty and trainees into clinical and psychologically supportive cohorts. Here we describe an adapted Firm System called the FitFirms, which focused on social connectivity and altruistic service as means to combat burnout in oncology trainees. Methods: We divided the Hematology and Oncology Division of an academic Comprehensive Cancer Care center into four cohorts of faculty-fellow teams called FitFirms. Each FitFirm was named after a notable local or national female leader in the field of cancer medicine—The Henrietta Lacks Firm, The Jane Wright Firm, The Padmini Iyer Firm, and The Rita Mehta Firm. The faculty and fellows interacted on an at-minimum quarterly basis in casual social events and/or community service-oriented events for 15 months. The social events included group dinners, bowling, paint and game nights. The service events included participation in 5K walk/run fundraiser for our institution’s cancer center and support of a National Cancer Survivors Day event for US Veterans. A didactic discussion series was created to explore concepts of resiliency, work-life balance, and the role of art in medicine—mentored by faculty across the spectrum of oncologic disciplines (Surgical Oncology, Gynecologic Oncology, Palliative Care, and Health Communication). The Maslach Burnout Inventory survey was used to survey the oncology trainees before and after the interventions. Results: Nine pre-intervention surveys were collected with 78% of trainees describing themselves as on the burnout spectrum of feeling either ineffective, overextended, disengaged, or burned out (22% engaged). After 15 months, 10 post-intervention surveys were collected in which 60% of trainees described themselves on the burnout spectrum (40% engaged). Conclusions: The FitFirms are a novel system using social capital to reduce the problem of burnout in oncology trainees by engaging in social connectivity and altruistic service through faculty-mentored, historically-named divisional cohorts.
Preoperative chemoradiation +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): A report from Children's Oncology Group (COG) and NRG Oncology.
Authors: Weiss Aaron R. , Chi Yueh-Yun , Chen Yen-Lin , Choy Edwin , Davis Jessica L. , Fanburg-Smith Julie , Hawkins Douglas S. , Kayton Mark , Million Lynn , Okuno Scott H. , Ostrenga Andrew , Randall R. Lor , Scharschmidt Thomas , Sorger Joel , Spunt Sheri L. , Tian Jing , Terezakis Stephanie Alicia , Wang Dian , Zambrano Eduardo , Black Jennifer O.
Published: March 2020

11002

Background: Pazopanib is a multi-targeted tyrosine kinase inhibitor with activity in advanced soft tissue sarcoma. ARST1321 is a phase II study designed to compare the near complete pathologic response rate (≥ 90% necrosis) of preoperative chemoradiation +/- pazopanib in children and adults with intermediate/high risk chemotherapy-sensitive NRSTS. Methods: ARST1321 is a jointly designed COG and NRG Oncology study opened to enrollment in July 2014. Eligible adult (≥18 years) and pediatric ( < 18 years) patients with unresected, newly diagnosed truncal/extremity NRSTS were enrolled into the Chemotherapy Cohort ( > 5 cm, grade 2/3, protocol-designated chemotherapy-sensitive histology). Following a dose-finding phase, patients were randomized to receive (Regimen A) or not receive (Regimen B) pazopanib ( < 18 years: 350 mg/m2/day; ≥ 18 years: 600 mg/day) in combination with ifosfamide (7.5 gm/m2/cycle) and doxorubicin (75 mg/m2/cycle) + 45 Gy preoperative RT followed by primary resection at week 13, then adjuvant chemotherapy. Results: As of June 30, 2018, 81 eligible patients were enrolled and randomized. Week 13 response is available for 42 patients (60% of expected information). The rate of ≥ 90% pathologic necrosis was 58.3% for Regimen A and 22.2% for Regimen B. Based on the significance level of 0.081 (for the second efficacy analysis with overall one-sided significance level of 0.20, power of 0.80, and O’Brien-Fleming-type cumulative error spending function), the 83.8% confidence interval for the difference was between 16.5% and 55.8%. At this predetermined interim analysis, the efficacy bound was crossed indicating that Regimen A is more efficacious than Regimen B. Given these findings, enrollment was stopped. Grade 3/4 toxicities were 73.8% for Regimen A and 29% for Regimen B with neutropenia, thrombocytopenia and febrile neutropenia being the most common toxicities. Conclusions: The rate of near complete pathologic response was significantly greater with the addition of pazopanib to preoperative chemoradiation in children and adults with intermediate/high risk NRSTS. The comparison of survival outcomes requires longer follow-up. Clinical trial information: NCT02180867.
Apatinib plus camrelizumab (SHR-1210) for unresectable high-grade osteosarcoma (APFAO) progressing after chemotherapy: A prospective, open label, phase II trial.
Authors: Xie Lu , Guo Wei , Xu Jie , Sun Xin , Liu Kuisheng , Zheng Bingxin , Ren Ting , Huang Yi , Tang Xiaodong , Yan Taiqiang , Yang Rongli , Sun Kunkun , Shen Danhua , Li Yuan
Published: March 2020

11013

Background: Results of previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy. Methods: We did this open-label phase 2 trial in Peking University People’s Hospital. We enrolled patients (≥14 years) with advanced osteosarcoma progressing after chemotherapy. Patients received 500 mg apatinib orally taken once daily plus 200 mg camrelizumab intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treatment. This trial is registered with ClinicalTrials.gov. (NCT03359018). Results: We enrolled 41 patients between January 1, and September 4, 2018. 20 (48.8%, 95%CI 32.8%-64.8%) of 41 patients were progression free at 6 months. Until final follow-up, the objective response rate was 21.95% (9/41). And the 6-m PFS rate and 4-m PFS rate were 54.32% (95% CI 37.62%-68.33%) and 70.00% (95% CI 53.24%–81.73%) respectively. Median PFS was 6.50 (95% CI 4.23–7.50) months while the median OS has not reached yet. And there were no statistical differences in the response rates or PFS between different PD-L1 expression groups ( P=0.153 and 0.231). Whereas target lesions with only pulmonary metastasis had obviously longer PFS than those lesions located at other places ( P <0.001). We also summarized all those lesions’ progression patterns as follows: slow pulmonary lesions’ progression(N=7), stable disease with lung but new lesions outside lung(N=4) and bone lesions’ progression(N=13), of which we found that there was obvious difference in PFS ( P=0.009) between different progression groups.Toxic effects led to dose reductions, or short interruptions, or both in 20 (48.78%) of 41 patients. There were no treatment-related deaths. Conclusions: The combination of apatinib and camrelizumab obviously prolonged PFS than single apatinib in the treatment for patients with advanced osteosarcoma progressing after chemotherapy. Those with pulmonary metastatic lesions obviously had longer PFS. Whether patients benefit from overall survival needs further observation. Clinical trial information: NCT03359018.
A three-gene signature to predict survival in pediatric osteosarcoma (OS) to follow patients toward liquid biopsy: A collaborative work in OS2006 protocol.
Authors: Entz-Werle Natacha , Tripp Aurelien , Weingertner Noëlle , Redini Francoise , Brouchet Anne , Gaspar Nathalie , Brugieres Laurence , Neumann Sophie Piperno , Marec-Berard Perrine , Dontenwill Monique
Published: March 2020

11014

Background: The survival of pediatric OS is stable worldwide since two decades. The management of OS is lacking new approaches to classify closely the patients and adapt thereafter the treatments. The objectives of our molecular study, using allelotyping, quantitative PCR (qPCR) and droplet digital PCR (ddPCR), were to determine the survival impact of tumor molecular profiling in the initial tumor biopsy, in the tumor resection after neoadjuvant chemotherapy and on circulating DNA at different treatment steps. The gene panel based on biomarkers of bone dedifferentiation was already identified in the large tumor cohort of the French national protocol OS94 and demonstrated a significant prognostic impact of 3 genes MET, TWIST and APC. To go further and understand its significance throughout protocols, the same study was performed in OS2006 tumors. Methods: We applied retrospectively in the cohort of OS2006 protocol (135 patients) the same molecular assessment comprising the targeting of those 3 genes with 3 techniques evaluating their rearrangement by allelotyping, their copy number variations by qPCR and ddPCR. A preliminary cohort of 20 patients with liquid biopsies at diagnosis, before tumor surgery and at the end of chemotherapy was screened by ddPCR. Results: We were able to determine frequent rearrangements in the regions containing these 3 genes and a statistically significant correlation was made between the presence of a gene rearrangement and a worst outcome. The 3-gene signature was significantly predicting the outcome of more than 85% of patients diagnosed for an OS. Furthermore, the persistence of those genes’ rearrangements in the primitive tumor after neoadjuvant chemotherapy comparatively to the initial biopsy was correlated to a higher risk of relapse. This 3-gene signature was also used for assessment of residual disease (RD) in liquid biopsies and was able to determine before tumor surgery the level of RD. Conclusions: This molecular signature seems to be clearly associated with patient outcome and was able to provide evidence that this approach is a powerful tool to be used in pediatric OS follow up to determine early relapse or progression.
Clinical characterization of patients with SDHC epimutation in gastrointestinal stromal tumors.
Authors: Ilanchezhian Maran , Fuller Sarah N. , Raygada Margarita , Stratakis Constantine A. , Meltzer Paul S. , Miettinen Markku , Glod John , Killian Keith , Arnaldez Fernanda Irene
Published: March 2020

11033

Background: Gastrointestinal Stromal Tumors are the most common malignancy in the GI tract. While the vast majority exhibit somatic mutations in KIT and PDGFRA, approximately 15% of GIST patients do not have this feature. This group of KIT and PDGFRA “wildtype” GISTs have in common a negative expression of SDHB when interrogated by immunohistochemistry. Succinate dehydrogenase (SDH) is a conserved enzyme that plays a critical role in cellular metabolism and energy production. A loss in SDH function is a mechanism observed in several types of cancers, and germline SDH mutations are considered a tumor predisposition syndrome. This group has reported that SDH-deficient gastrointestinal stromal tumors often harbor germline mutations in the SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx). There is, however, a defined group that shows lack of SDH expression in the absence of mutation. Methods: We performed targeted exome sequencing on GIST patients’ tumor samples from the NIH GIST clinic and identified 25 SDHx-WT cases. Genome-wide DNA methylation and expression profiling showed SDHC promoter-specific CpG island hypermethylation and gene silencing in these 25 SDHx-WT, SDH deficient GISTs. Results: Clinical characterization of this cohort revealed that 24 of 25 SDHC-epimutant GISTs occurred in female patients, with a median age of 12 upon diagnosis. The median tumor size of this cohort of patients was 4.0 cm. Of the 16 patients from whom we were able to obtain complete pathology data, 15 showed epithelioid or mixed-epithelioid tumor morphology. All of them showed negative immunohistochemical staining for SDHB. 15 of 16 patients had multifocal tumors, which is a common finding in this population. Conclusions: The profiling of this cohort provides further insights into the natural history and pathogenesis of SDHC-epimutant GIST tumors.
Correlation of imatinib plasma trough concentrations with adverse reaction in Chinese gastrointestinal stromal tumors patients.
Authors: Xia Yanzhe , Chen Sile , Cai Shirong , He Yulong , Zhang Xinhua
Published: March 2020

11034

Background: Imatinib is the standard treatment for patients of Gastrointestinal Stromal Tumors (GISTs), but the intra- and inter-variability of imatinib plasma trough concentration (Cmin) are significant. Few studies investigated the association between Cmin and adverse reaction in Chinese GIST patients. The distribution of imatinib Cmin in different doses and the correlation of imatinib Cmin with adverse reaction in Chinese GIST patients from a high-volume center were evaluated. Methods: From 1 Jul 2017 to 31 Dec 2018, a total of 400 patients who were under imatinib treatment were prospectively studied. All patients’ informed consents were obtained. Steady state plasma samples were obtained from patients at least administrating 1 month treatment who were taking imatinib 100 to 800 mg/d, with continuous similar timing of daily dosage for more than 14 days. The adverse reaction was recorded during regular follow-up at out-patient clinic, and blood sample was collected 22±2 hours to the next dosage of imatinib. Liquid chromatography tandem mass spectrometry was applied to determine the concentration. Adverse reaction grades were referred to CTCAE v4.0. Results: A total of 368 patients who followed the same dose of imatinib with good compliance, and having at least 2 times of tests were investigated. The imatinib Cmin was 384±53 ng/mL, 776±337 ng/mL, 986±327 ng/mL, 1078±498 ng/mL, 1309±712 ng/mL, 1620±469 ng/mL, 2117±597 ng/mL and 3844±987 ng/mL in patients who were administrated with 100 mg/d (n = 3), 200 mg/d (n = 15), 250 mg/d (n = 5), 300 mg/d (n = 80), 400 mg/d (n = 235), 500 mg/d (n = 3), 600 mg/d (n = 22) and 800 mg/d (n = 5), respectively. In correlation analysis, imatinib Cmin was significantly correlated with periorbital and limbs edema (p < 0.01), anemia (p < 0.01) and rush (p < 0.01), correlated with diarrhea and conjunctival hemorrhage but not significant. Much higher Cmin was observed in severe adverse reaction (≥ grade 3) of periorbital and limbs edema and rash. There was no correlation between Cmin with leukopenia, nausea, vomiting, muscle cramp or hepatobiliary disorders. Conclusions: In Chinese GIST patients, imatinib Cmin at steady state was seems higher than Western populations previous reported, especially in higher doses (≥600 mg/d). Imatinib Cmin was correlated with anemia, periorbital and limbs edema, diarrhea and conjunctival hemorrhage, suggesting that imatinib Cmin monitor might be considered when patients were subjected to severe adverse reactions which were caused by excessive imatinib plasma concentration.
Multicenter phase II trial of pazopanib (P) in patients with angiosarcoma (AS).
Authors: von Mehren Margaret , Litwin Samuel , Ravi Vinod , Schuetze Scott , Movva Sujana , Agulnik Mark , Kraft Andrew S. , Tetzlaff Eric Daniel , Somaiah Neeta
Published: March 2020

11039

Background: AS is a rare aggressive soft tissue sarcoma derived from endothelial cells. It can occur as cutaneous or visceral disease, be associated with chronic lymphedema, or arise after radiation therapy. Non-metastatic AS has a poor overall 5-year survival rate of 27-35%; improved treatments are needed. We hypothesized that P would have therapeutic activity in AS because of the agent’s anti-angiogenic activity. Methods: This was an open label, multi-institutional trial of P using a Simon two-stage design. The primary endpoint was to determine the PFS at 3 months and response rate defined as CR and PR in AS treated with P. Eligibility criteria included incurable AS, age≥18, adequate blood counts, cardiac, hepatic and renal function, RECIST measurable disease, ability to swallow pills and provide informed consent. P was given as 400 mg orally twice daily, with ongoing disease assessment every 8 weeks. Results: From 11/2011 - 12/2018, Twenty-nine patients were treated on study (Table; data available for 28 patients). 50% were female and 55% had cutaneous disease. Eight patients were inevaluable for response: 3 never started P (lab abnormalities day 1, n=1; consent withdrawal, n=2); 4 due to toxicity, 1 for non-compliance. As of 12/15/18, best response was SD seen in 12 patients. The 3-month PFS rate determined by Kaplan-Meyer estimate was 54.6% (95%CI 36.0, 82.9%). SD was seen in 25% (4/16) with cutaneous disease and 8.3% (1/12) with visceral disease. Toxicities were manageable and similar to prior reports. Grade 3/4 toxicities included hypokalemia, increased U/P ration, lymphocytopenia, hypertension and abnormal LFTs; there was one death due to cardiac arrest considered possibly related to P. Conclusions: Accrual rate was slower than expected possibly because P was available off-study. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were limited by early withdrawal of patients. No RECIST responses were observed; however P has a clinically meaningful 3-month PFS, primarily in cutaneous AS. Clinical trial information: NCT01462630. [Table: see text]
Retroperitoneal soft tissue sarcoma (RPS): Recent outcome improvement and refinement of treatment strategies at a single institution.
Authors: Fiore Marco , Almond Max , Barretta Francesco , Callegaro Dario , Colombo Chiara , Radaelli Stefano , Pasquali Sandro , Barisella Marta , Morosi Carlo , Sanfilippo Roberta , Sangalli Claudia , Stacchiotti Silvia , Miceli Rosalba , Casali Paolo Giovanni , Gronchi Alessandro
Published: March 2020

11041

Background: Extended surgery in retroperitoneal sarcoma (RPS) has resulted in less recurrences and better survival. We investigated whether outcome further improved, after the recent understanding of behavior of different RPS subtypes and introduction of multimodal therapies. Methods: Consecutive primary RPS operated at a single center were analyzed comparing 3 periods (2002-2006; 2007-2011; 2012-2016). Primary endpoints were overall survival (OS), crude cumulative incidence (CCI) of local recurrence and distant metastasis (LR, DM) for each subgroup: well differentiated (WDLPS), dedifferentiated G2 (G2DDLPS), G3 (G3DDLPS) liposarcoma, and leiomyosarcoma (LMS). Secondary endpoints: morbidity and post-relapse OS. Fisher/Chi-squared and Cochran–Armitage trends test were used. Survival was analysed by Kaplan-Meier/Cox PH or CCI/Fine Gray models in the competitive risk framework and compared with log-rank/Wald Gray tests. Multivariable analyses were performed. Results: Overall 437 RPS were operated: 82, 128 and 227 in the 1st, 2nd and 3rd period. Median follow-up was 125, 86 and 39 months. Complete resection (R0/R1) improved from 93.9% to 98.2% (p=0.059), median number of resected organs increased from 2 to 4 (p<.0001). Postoperative morbidity did not change (18.3%, 16.4%, 22.5%; p=0.269). Administration of radiotherapy and chemotherapy (CT) differed over time according to different subtypes. 5-yr OS improved (63.2% to 74.7%, p=0.005), along with a non-significant reduction in LR CCI (18.2% to 16.4%, p=0.379) and no change in DM CCI. At multivariable analysis, study period remained an independent prognostic factor for OS among the other known risk factors (3rd vs 1st period HR: 0.33, p<0.001). Subgroup analysis showed the following associations with better prognosis: 1. Improvement in 5-yr OS (from 55.0% to 70.7%, p=0.024) and LR (from 45.0% to 19.8%, p=0.060) in G2DDLPS, associated with more organs resected 2. Improvement in 5-yr OS (from 18.2% to 49.7%, p=0.035) and DM (from 70.0% to 19.8%; p=0.015) in G3DDLPS, associated with more anthracycline-based CT 3. A better 2-yr post-relapse OS (from 46.3% to 65.2%, p=0.122). Conclusions: OS of patients with DDLPS improved over time: in G2 this was associated with a refinement in the surgical approach, while in G3 with a more liberal use of anthracycline-based CT. New available therapies for recurring RPS may also have extended post-relapse OS. Prospective studies on perioperative CT for high risk RPS subtypes are eagerly awaited.
Complete remission of patients with heavily pretreated uterine sarcomas by weekly bevacizumab and temozolomide.
Authors: Takasaki Kazuki , Ikeda Sayaka , Matsuura Hiroko , Kudoh Kazuya , Yoshikawa Tomoyuki , Kouta Hiroko , Takano Masashi , Kikuchi Ryoko , Horikoshi Miyuki , Kikuchi Yoshihiro
Published: March 2020

11051

Background: Uterine sarcomas are associated with poor prognosis snce the complete remission is extreme rare. Therefore, treatment with chemotherapy including eribulin or trabectedin, hormone therapy or molecular-targeted therapy including pazopanib or olaratumab was expectd, but the effect is not satisfactory. Thus, we evaluated the effects of temozoromide (T), derivateives of dacarbazine, and bevacizumab (B) (TB) containing or not cabozantinib (C), a multikinase inhibitor of MET, AXL, RET and VEGFR2 (TBC) in heavily pretreated cases of uterine sarcomas. Methods: From 2009 to 2018, 29 patients (pts) with heavily pretreated uterine sarcomas were enrolled. Fifteen of 29 patients were treated with T (80mg/body/day) and B (2mg/kg; days1, 8 and 15, q 4 weeks) (TB). Since 2013, C (140mg/body/week) was added to TB (TBC, n = 14). Treatment was continued until disease progression and/or unmanageable toxicities. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) v1.1, and adverse events were assessed by common terminology criteria for adverse events (CTCAE) v4.0. Results: Seven pts (24 %) had carcinosarcoma, fifteen (52 %) had leiomyosarcoma, five (17 %) had undifferentiated uterine sarcoma, one (3 %) had adenosarcoma, and one (3 %) had uterine sarcoma-not other specified. Twenty-three of 29 pts were subjected to response evaluation. Five pts (22 %) had complete response (CR), three (13 %) had partial response, six (26 %) had stable disease (SD). The response rate (RR: CR+PR) and disease-control rate (DCR: CR+PR+SD) were 35 % and 70 %, respectively. The median progression-free survival was 6.5 (2-89) months. When adding C to T and B, DCR was improved from 64 % (TB) to 75% (TBC). Median administration of cycles is 7 (TB) and 5 (TBC). There were 2 dead cases from perforation, but toxicity was almost mild and manageable. Conclusions: We have experienced 5 cases of CR by TB or TBC. Moreover, addition of C to T and B resulted in better disease-control rate. Compared to other reported treatment, TB combined with C could be substantially effective in cases with heavily pretreated uterine sarcomas. These results warrant further prospective and randomized studies.