bluuebunny/crossref_metadata_2025 huggingface dataset:
Authorship gender equity in global oncology publications.
Authors: Hornstein Paula , Tuyishime Hubert , Mutebi Miriam Claire , Lasebikan Nwamaka , Rubagumya Fidel , Fadelu Temidayo
Published: June 2021

11008

Background: There is increasing recognition of authorship inequity in academic medicine specialty publications. Analyses in other specialties note that female authors consistently comprise a minority of the first authors and an even smaller percentage of last authors. While this trend may be improving, we hypothesize that significant authorship gender disparities still exist in global oncology journals. Methods: This study comprehensively analyzes the gender distribution of authors for articles published in the Journal of Clinical Oncology Global Oncology (JCO GO), a premier journal in the field, from its inauguration in 2016 to March 2020. A total of 608 articles were identified as matching one of the following six article types: original report, editorial, commentary, case report, special article, and review article. We collected data such as the author’s position, gender, institutional affiliation, and country affiliation. Author gender was categorized as male, female, or indeterminate based on first name probabilities assessed by genderize.io, with a threshold probability of 0.8 based on prior studies. Authorship distribution was analyzed by region and country income level according to the World Bank classification. Results: Of the 608 article first authors, 47.5% were identified as male, while 41.4% were female. Male authors made up a comparatively higher proportion of the 592 last authors; 57.1% were identified as male compared to 32.1% who were female. A similar trend was seen among the 4102 middle authors; 51.4% were identified as male and 38.1% were female. The percentage of authors deemed indeterminate in the cohort was less than 11%. Female authors were more underrepresented among authors from low-income countries; they made up 21.6% of first authors and 9.1% of last authors. Authorship gender by world regions is summarized in Table below. Conclusions: Our analysis shows that authorship inequities persist in global oncology publications. Female authors from lower-income countries, and regions in Sub-Saharan Africa and South Asia, were markedly underrepresented. The underlying reasons for underrepresentation of female authors are multifactorial; further studies are needed to elucidate these factors and to develop and evaluate mitigating strategies.[Table: see text]
The positive impact of mentoring on burnout: Organizational research and best practice interventions for cancer hospital employees.
Authors: Cavanaugh Katelyn , Belfer Bret , Cline Debbie , Holladay Courtney , Pickard Todd Alan , Thoman Evan , Chang Shine
Published: June 2021

11012

Background: While burnout is not a new concept, combating it is becoming an increasingly important focus for organizations across all industries. Recently, the World Health Organization recognized burnout as an “occupational phenomenon” (WHO, 2019), and it was included in the 11th Revision of the International Classification of Diseases, where it is defined as “a syndrome conceptualized as resulting from chronic workplace stress that has not been successfully managed.” The University of Texas MD Anderson Cancer Center addresses burnout at the institutional level in support of all 22,000 workforce members. One avenue of this work focuses on mentoring. Mentorship, both formal and informal, has demonstrated positive effects to include empirical investigations that demonstrate its benefit in reducing risk of burnout in multiple settings for a variety of audiences (Qian et al., 2014; Thomas & Lankau, 2009; van Emmerik, 2004; Varghese at al., 2020). Although mentoring is not as flashy as other interventions, what the last year has shown is that people need human connection now more than ever. Methods: In order to investigate the relationship between burnout and mentoring in our organization, we analyzed responses to our biennial voluntary employee survey, in which all employees were asked whether they are involved in a mentoring relationship and completed a single-item burnout scale. Results: We analyzed the survey data using a chi-square test and found that employees participating in mentoring relationships were less likely to report burnout than employees who are not participating in a mentoring relationship, χ2 (1, 14,486) = 17.431, p < 0.005. The same pattern held for all types of employees; faculty, classified staff, leaders, clinical employees, and non-clinical employees, indicating that the experience of mentorship may be universal regardless of role, rank, and type of work. We suspect that the benefits of mentoring are bi-directional for mentors and mentees, though this should be investigated directly. Conclusions: Both formal and informal types of mentoring programs exist within MD Anderson to support retention, professional fulfillment, and reduce burnout. All employees have access to a centralized online mentoring platform to find a mentor. Formal mentoring support is also provided through various programs developed for specific professional cohorts, including physicians, advanced practice providers, and registered nurses. In addition, informal mentoring support is offered in the form of employee volunteer wellness champions. Together, these formal and informal mentoring programs have positively influenced burnout across the organization.[Table: see text]
A pilot study to prevent burnout in junior oncology doctors during the COVID-19 pandemic in a tertiary U.K. center.
Authors: So Alfred Chung Pui , Hunter Sarah , Chan Karen , Rigg Anne Sagar , Smith Sue , Miller Raselle , Thillai Kiruthikah
Published: June 2021

11015

Background: Burnout is a syndrome defined by emotional exhaustion, depersonalisation and loss of personal accomplishment. It is a growing concern amongst doctors, particularly in oncology, who face the added stress of delivering life changing results to patients and managing end of life care. This has potential for negatively impacting mental health, job satisfaction and ultimately patient care. This has been compounded by the COVID-19 pandemic and the uncertainty around complex oncological treatment decisions, longer working hours, redeployment, and constant changes to working patterns to meet the evolving clinical need. In response to this, a novel wellbeing intervention was designed by the educational lead consultant and psychologists to prevent burnout during the pandemic. Methods: Junior doctors working at a single UK cancer centre during the COVID-19 pandemic were invited to attend weekly 30 minute wellbeing sessions facilitated by a clinical psychologist throughout their oncology placement (average 4-6 months). Sessions had an average attendance of 3-6 doctors and began with a 5 minute breathing and relaxation exercise followed by a mixture of clinical debriefing, reflective practice, and mindfulness strategies. Trainees were invited to have individual sessions if required. Surveys based on the 14 point Warwick Edinburgh Well Being Scale (WEMWBS) were conducted at the start and end of placement. Additional qualitative feedback was collated. Results: Throughout a 6 month period, 10 doctors participated in this study. Baseline WEMWBS scores revealed average mental wellbeing (n = 8), high mental wellbeing (n = 1) and probable depression (n = 1). Median baseline WEMWBS score was 52(41-62). Median number of sessions attended was 11(3-14). Post intervention, there was no significant deterioration in baseline WEMWBS score (mean change +2.2; p= 0.34). When doctors were asked about their optimism for the future, there was a significant increase by +0.4 points ( p= 0.037). With respect to participant feedback, 100% were either ‘satisfied’ (n = 1) or ’very satisfied’ (n = 9) with the group facilitation and 100% found the group sessions either ‘helpful’ (n = 7) or ‘very helpful’ (n = 3). Trainee feedback described the benefits of reflecting in a structured and safe environment, breathing exercises, and learning mindfulness strategies. Conclusions: Burnout is a serious concern amongst junior oncologists and is rising as a result of COVID-19. We present a novel intervention that promoted psychological flexibility and importantly maintained mental wellbeing throughout the pandemic. Further studies are planned to develop evidence based interventions to tackle this important issue.
Moral distress, organizational climate, and the risk of burnout among oncology physician assistants.
Authors: Tetzlaff Eric Daniel , Hylton Heather Marie , Ruth Karen , Hasse Zachary , Hall Michael J.
Published: June 2021

11018

Background: Moral Distress (MD) is the result of barriers or constraints that prevent providers from carrying out what they believe to be ethically appropriate care and has been associated with burnout. Advances have been made in our understanding of burnout in the oncology (Onc) workforce but our understanding of MD remains limited. This study was initiated to explore associations between moral distress, burnout, and the organizational climate (OC) for Onc Physician Assistants (PAs). Methods: A national survey of onc PAs was conducted in 2020. MD and Burnout were assessed with the Maslach Burnout Inventory and the Measure of MD – Healthcare Professionals (MMD-HP). To assess OC, the Nurse Practitioner Primary Care OC Questionnaire (NP-PCOCQ) was revised for Onc PAs and assessed professional visibility (PV), administrative relations (AR), physician relations (PR), and professional autonomy and support (PAS). A robust Poisson regression model was used to estimate risk ratios (RR) for burnout associated with MD and OC variables. Results: Respondents who completed the survey included 146 Onc PAs that were mostly female (90%), White/Caucasian (84%), married/partnered (78%), and in medical Onc (73%). Mean MMD-HP score was 71.5 and burnout was reported by 39.7% of PAs. MMD-HP scores did not differ based on specialty, practice setting or practice type. PCOCQ subscale scores were lower for PAs with burnout vs. without burnout (p=0.003 to p < 0.001). Increasing levels of MD were associated with increased levels of emotional exhaustion (p<0.001), depersonalization (p<0.001) and a higher overall rate of burnout. For Low, Medium and High MMD, burnout rates were 10%, 44% and 66% respectively (p<0.001). Risk of burnout was associated with increasing levels of MD, which remained when adjusted for the PCOCQ subscales. An interaction model with the PCOCQ subscales and the association between burnout and MD was not significant. Conclusions: Higher levels of MD and unfavorable organizational climate are associated with Onc PA burnout. The relationship between MD and burnout does not appear to be moderated by organizational climate. Additional research is needed to identify potential moderators of the MD/Burnout relationship. Risk Ratio estimate for Burnout.[Table: see text]
Hematology/medical oncology fellow responses to the initial development of an antiracism curriculum.
Authors: Nakajima Erica C. , Messmer Marcus , Jones Jennifer Marie , Mathieu Luckson , Phillips Tanyanika , Weekes Colin D. , Marshall Catherine Handy , Sanderford Honor , Donehower Ross C. , Marrone Kristen , Moyo Victor M.
Published: June 2021

11042

Background: While the American Council on Graduate Medical Education (ACGME) set up a Planning Committee for Diversity in GME in 2018, no formalized milestones or training mandates have been announced. The nation-wide protests for racial justice following the senseless killings of Breonna Taylor, Ahmaud Arbery and George Floyd further brought to the forefront the need for immediate action to address widespread inequities across graduate medical education, our healthcare system and society as a whole. Therefore, the Johns Hopkins Hematology/Medical Oncology Fellowship Program focused on creating an anti-racism curriculum to foster dialogue on systemic racism and discrimination, grounded in the institutional and geographic context of our training program. Methods: Using the Kern six step curriculum development method, we created a comprehensive anti-racism initiative, which included virtual townhalls with Black alumni of the fellowship, book clubs, readings, and lectures. We sought to deepen the fellowship’s awareness of the impact of racism and inequity upon trainees, underrepresented minority oncologists and hematologists, and patients in order to develop initiatives to confront them productively. Trainees received a survey 6 months after the start of the curriculum to assess the impact of the initiatives upon trainees, and inform iterative changes to the curriculum. Results: 25 of 34 fellows across all post-graduate years (PGY) completed the survey. Fellows agreed that the curriculum was helpful (68%) and encouraging (60%). Collectively, fellows reported that the curriculum increased their awareness of instances of racism in medicine, caused them to think about next steps that the fellowship could take to address racism, and enabled them to identify available resources for support and further education. Respondents selected community engagement and recruitment of diverse fellowship classes as the most pressing priorities for the program. Conclusions: Social justice and anti-racism education belong in the formalized training of our hematology/medical oncology fellows. To this end, our ongoing curricular expansion is focusing on anti-racism training, diverse recruitment and youth mentorship. Collectively, a comprehensive yet program-specific approach facilitates opportunities for learning, engagement and development of the skills necessary to engage in this life-long work for ourselves, our communities and our patients.
A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma.
Authors: Van Tine Brian Andrew , Chawla Sant P. , Trent Jonathan C. , Wilky Breelyn A. , Chugh Rashmi , Chmielowski Bartosz , Kummar Shivaani , Basu Mallick Atrayee , Somaiah Neeta , Cranmer Lee D. , Agulnik Mark , Keedy Vicki Leigh , Stacchiotti Silvia , Vincenzi Bruno , Badalamenti Giuseppe , Siontis Brittany L , Attia Steven
Published: June 2021

11505

Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.
Outcomes in the dedifferentiated liposarcoma cohort of SAR-096, a phase II trial of ribociclib in combination with everolimus in advanced dedifferentiated liposarcoma (DDL), and leiomyosarcoma (LMS).
Authors: von Mehren Margaret , Movva Sujana , Handorf Elizabeth A. , Merriam Priscilla , Morgan Jeffrey A. , Choy Edwin , Tetzlaff Eric Daniel , Barker Emma , Harley Allisa Cherae , King April , Matloob Sahar , Jerome Erika , Rink Lori , George Suzanne
Published: June 2021

11515

Background: Dedifferentiated liposarcoma (DDL) is characterized by ring chromosomes of chromosone12, which includes amplification of MDM2 and CDK4. Exposure to CDK4 inhibitors in Rb+ leiomyosarcoma (LMS) cell lines leads to decreased cell proliferation, and increased senescence, and G0/G1-phase arrest. When combined, ribociclib a CDK4 inhibitor and everolimus, an mTOR inhibitor show synergistic growth inhibition in multiple tumor models. We hypothesized that this combination could lead to increased disease control in patients with DDL. Methods: This study enrolled patients (pts) into one of two cohorts: DDL or Rb+ LMS. LMS pts were required to have 1 prior line of therapy; DDL pts required no prior therapy. There were no limits to prior therapies in either group. Measurable disease by RECIST 1.1 was also required. Ribociclib was given at 300 mg daily for 21/28 days and everolimus was given continuously at 2.5 mg daily in 28 day cycles. The primary endpoint was progression free rate at 16 weeks. A Simon two-stage design was utilized and if at least 8 out of 24 pts were progression free at 16 weeks, the treatment was declared promising for the cohort. Here in we present data on the DDL cohort. Results: To date, 21 DDS pts, median age of 63 (range 40-79), of which 43% (n = 9) female were treated. Median prior lines of therapy was 1 (range 0-6). Of 19 pts with complete data, 8 (42%) met the primary endpoint of non-progression at 16 weeks. Confirmed partial response was seen in 2 pts (10%). Median PFS was 16 weeks, and stable disease occurring as best response in 11 (55%) pts. Grade 3-4 toxicities were uncommon except for lymphopenia (24%) and neutropenia (33%); no episode of neutropenic fever were observed. There was one death on study secondary to myocardial infarction, considered possibly related to therapy. Results of optional tissue biopsies pre and on therapy obtained to assess pharmacodynamic changes in PTEN, pAKT, CDK4, Rb and pS6 will be presented. Conclusions: The combination of ribociclib and everolimus demonstrates activity in DDL with prolonged stable disease (>16 weeks) meeting the primary protocol endpoint. Notably partial responses were also observed. The combination was well tolerated with acceptable side effects. Updated outcomes will be presented. Clinical trial information: NCT03114527.
Giant cell tumor of bone: Effect of longer dosing intervals of denosumab on tumor control and bone related complications.
Authors: Jiang Cindy , Zhao Lili , Schuetze Scott , Chugh Rashmi
Published: June 2021

11525

Background: Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone neoplasm characterized by osteoclast activation causing destructive osteolysis. Denosumab, a human monoclonal antibody against RANK ligand, has emerged as an effective treatment option when surgery is not recommended, but can cause significant bone toxicity. Current standard dosing is every 4 weeks after 3 weekly loading doses. As patients (pts) with GCTB are often young adults, frequent denosumab administration long-term may be burdensome and associated with increased risk of complications. We assessed whether alternative, longer dosing intervals are associated with differences in efficacy or bone toxicity. Methods: Retrospective chart review was conducted on GCTB pts over 18 years old at University of Michigan who received at least 1 year of standard denosumab treatment. Pts were identified using a free-text medical record search engine with keywords “giant cell tumor” and “denosumab” until August 2020. We compared bone-related adverse effects and tumor control in pts who continued denosumab every 4 weeks versus longer treatment intervals. Decision to increase interval between doses was based on provider and pt discussion and preference as part of routine medical care. Results: 37 GCTB pts were identified; 51% female and 49% male. Average age was 41 years (range 22-73). Most common primary location was lower extremity (38%), followed by pelvis (35%), upper extremity (14%), spine (8%), and head/neck (5%). Metastasis were present at start of treatment in 14% of pts, involving lung (n = 4) and spine (n = 1). Pts received median of 71 (range 15-139) total doses of denosumab. Dosing interval was increased in 38% (n = 14). With the first interval change, 43% changed to every 6 weeks, 29% every 8 weeks, and 29% every 12 weeks dosing. Most common final dosing interval was 12 weeks (n = 8). 6 pts (16%) had bone complications after mean of 56 doses. This included osteonecrosis of the jaw (n = 4), atypical fracture (n = 1), and non-healing dental wounds (n = 2). All pts with bone complications were treated on the monthly dosing schedule, but there was no statistically significant difference compared to longer intervals (p = 0.22). Pts with GCT progression (n = 10) were either no longer receiving therapy or had missed denosumab doses. There was no statistically significant difference in PFS with standard vs. interval increased dosing (p = 0.97). However, 5-year PFS was superior with interval increased vs standard dosing (p = 0.036). Conclusions: Increasing the interval of denosumab dosing for GCTB provided similar tumor control as compared to standard dosing and is potentially associated with less bone toxicity and more convenience for afflicted pts. Further larger scale studies are needed to better define the optimal interval of denosumab administration in GCTB and the effect on efficacy, toxicity, and associated health care expense.
Efficacy and safety of JMT103 in patients with giant cell tumor of bone: A multicenter, single-arm, open-label, phase Ib/II study.
Authors: Niu Xiaohui , Wei Feng , Tu Chongqi , Huang Gang , Bi Wenzhi , Li Jianmin , Yao Weitao , Zhang Xiaojing , Shen Jingnan , Zhang Guochuan , Yan Wangjun , Yang Jilong , Lin Jianhua , Ye Zhaoming , Wang Dong , Guo Zheng , Tong Zhichao , Zhou Yuhong , Xu Hairong , Li Tao
Published: June 2021

11526

Background: JMT103 is a novel, fully humanized IgG4 monoclonal antibody targeting RANKL, inhibiting osteoclastogenesis and osteoclast-mediated bone resorption. A multicenter, single-arm, open-label, phase Ib/II study was conducted to evaluate the efficacy and safety of JMT103 in patients (pts) with Giant cell tumor of bone (GCTB). Methods: Eligible pts (ECOG: 0-2) were adults with pathologically confirmed unresectable GCTB or their planned surgery is associated with severe morbidity. Pts with active dental or jaw condition requiring oral surgery, other anti-tumor therapies, anti-RANKL antibody or concurrent use of bisphosphonates were excluded. 2 mg/kg JMT103 was administrated subcutaneously every 4 weeks with a loading dose on days 8 and day 15 of the first 4 week of therapy. The primary endpoint was tumor response, defined as elimination of at least 90% giant cells or objective response of the target lesion assessed by radiologic imaging as per Modified Inverse Choi density/size (ICDS) or the Modified European Organization for Research and Treatment of Cancer (EORTC) criteria within 12 weeks. Secondary endpoints included safety profile, change of pain score using Brief Pain Inventory-Short Form, and suppression of bone-resorption biomarkers. Results: 38 pts (14 males) were enrolled between June 3 and December 24, 2020. The median age was 31 years (range 18-57). Lesions sites included lower extremities (39.5%), upper extremities (31.6%), spine (21.1%) and pelvis (13.2%). Among 32 pts with at least 1 efficacy evaluation within 12 weeks, 26 (81.3%, 95% CI: 63.6-92.8) had a tumor response by at least one response criteria. All 7 pts who underwent histological assessments had a tumor response. 25 of 32 pts assessed by radiology had a tumor response. As per ICDS criteria, 23 of 32 (71.9%) had a response; as per EORTC criteria, 15 of 17 (88.2%) had a response. 21 of 26 (80.8%) pts who complained of pain at baseline experienced reduced pain during the treatment. The median reductions in bone-resorption biomarkers were 71.8% (IQR 67.7-82.4) for uNTx/Cr (p < 0.001) and 81.4% (IQR 68.3-84.7) for sCTx (p < 0.001) at day 8. Of all 38 pts who were included in safety analyses, treatment-related adverse events (TRAEs) occurred in 14 pts. The most common TRAEs were hypophosphatemia (18.4%), hypocalcemia (7.9%) and blood bilirubin increased (7.9%). 1 patient (2.6%) was reported a grade 3 AE but it was not related to the treatment; other AEs were grade 1–2. Conclusions: JMT103 demonstrated encouraging anti-tumor efficacy and manageable safety profile in pts with unresectable GCTB or at high risk of severe morbidity after surgery. Clinical trial information: NCT04255576.
A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.
Authors: Serrano Cesar , Valverde Claudia , Cruz Jurado Josefina , Martinez-Trufero Javier , Guri Xavier , Giuppi Martina , Redondo Andrés , Suarez-Paniagua Beatriz , Romagosa Cleofe , Martinez Virginia
Published: June 2021

11534

Background: KIT or PDGFRA oncogenic activation drives GIST progression throughout the disease course. Accordingly, currently approved agents in metastatic GIST focus on the therapeutic suppression of these receptors. However, the clinical benefit after imatinib (IM) progression is still modest, suggesting the co-operation of KIT/PDGFRA-independent mechanisms in GIST cell survival. Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, and preclinical studies evidenced antitumoral activity in GIST as single agent and in combination with IM in both IM-sensitive and IM-resistant models. Methods: The phase Ib portion studied IM 400 mg daily plus weekly selinexor in patients (pts) with IM-resistant, advanced GIST. Prior intolerance to IM was not allowed. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Investigator-assessed response was evaluated every 8 weeks using RECIST 1.1. Results: At data cutoff of Sep 25, 2020, 12 pts were enrolled and received treatment with IM 400 mg and selinexor once weekly at dose levels (DL) 1 (60 mg), DL2 (80 mg) and DL3 (100 mg). Median age 57 (range 46-77), 42% female, median prior therapies 4 (range 2-7). Although only 1/6 pts developed a dose limiting toxicity (DLT) at DL3, the RP2D was defined at DL2 (IM 400 mg daily and selinexor 80 mg once weekly) based on activity data in the DL2 and the need for dose reductions in 5/6 pts at DL3 after the DLT window. All pts were evaluable for toxicity and response. One DLT occurred at DL3 (G3 nausea). Non-DLT G3/4 toxicities were anemia (1/12 pts), neutropenia (1/12 pts), vomiting (1/12 pts) and fatigue (2/12 pts). Common G1/2 toxicities were nausea (11/12 pts), vomiting (10/12 pts), neutropenia (5/12 pts) and anemia, fatigue, diarrhea, and periorbital edema (4/12 pts each). No unexpected toxicities were observed. Overall response rate in the 12 pts evaluable for response was 67% (95% CI 0.349-0.901), with 2 pts achieving PR (17%) and 6 pts SD (50%) as the best response. Clinical benefit rate (CBR = CR, PR, SD) ≥ 16 weeks was 42% (95% CI 0.157-0.723). Median progression free survival was 3.5 months (95% CI 1.7-7.3). Four pts remain on trial at data cutoff. Conclusions: IM and selinexor combination is well-tolerated and has clinical activity in heavily pretreated GIST pts. The trial is currently exploring selinexor as single agent in the IM-resistant GIST population. Clinical trial information: NCT04138381.
Next generation sequencing of sarcomas: Response to crizotinib in two cases with MET amplification.
Authors: Victor Adrienne I. , Alvarez Olga , Baumgart Megan Ann , Goyal Gaurav , Sahasrabudhe Deepak M.
Published: June 2021

11538

Background: Sarcoma subtypes are often defined by recurrent molecular alterations. The purpose of this study is to review the utility of next generation sequencing (NGS) in sarcoma patients and report clinical outcomes to matched therapies. Methods: The records of all patients seen at the University of Rochester Medical Center (URMC) with sarcoma and NGS profiling between 8/2013 and 3/2020 were reviewed. Responses to agents targeting reported alterations were analyzed. In patients with fluorescent-in-situ hybridization (FISH) testing, fusion events by NGS were compared with FISH results. All highlighted pathogenic alterations on the NGS profile report as well as variants of uncertain significance (VUS) were recorded. Results: Seventy-five patients met inclusion criteria. Of these, 25 received a treatment based on identified alterations; 1 had a complete response (CR), 4 had partial responses (PR), and 4 experienced disease stabilization (SD). We identified two patients with MET amplified sarcoma that responded to treatment with crizotinib. One other patient with a diagnosis of leiomyosarcoma was found to have an unusually high total mutational burden (TMB) and experienced complete pathologic response to dual checkpoint blockade. In 4 cases, testing resulted in a change in subtype diagnosis. Several rare and novel fusions were identified; a sarcoma with TPM4-NTRK3 fusion responded to larotrectinib, while a sarcoma with PML-JAK1 fusion did not respond to ruxolitinib, and a sarcoma with IL7R-BCL2 fusion progressed on venetoclax. Table summarizes matched therapies in responders. Conclusions: NGS profiling led to a targeted therapy with a clinical benefit rate of 12% in this cohort. NGS profiling led to a change in diagnosis in 5% of this cohort. Multi-institutional collaborations to track outcomes of matched therapy would help determine the utility of therapies in rare cancers and unusual alterations.[Table: see text]
VAC temporization pending final margins after suprafascial myxofibrosarcoma excision to reduce the rate of local recurrence.
Authors: Fourman Mitchell Stephen , Ramsey Duncan C. , Kleiner Justin , Daud Anser , Newman Erik T. , Schwab Joseph H. , Chen Yen-Lin , DeLaney Thomas F. , Mullen John Thomas , Raskin Kevin , Lozano-Calderon Santiago
Published: June 2021

11573

Background: The microinvasive nature of suprafascial myxofibrosarcoma complicates the accuracy of intraoperative margin assessment, and tumor bed resections after soft tissue reconstruction are unreliable. For the past 3 years we have temporized the excised tumor bed with a wound VAC, delaying soft tissue coverage until final negative margins were achieved. Here, we compare the oncologic/surgical outcomes of suprafascial myxofibrosarcomas managed with VAC temporization (VT) with single-stage excision/reconstruction (SS). Methods: We retrospectively studied suprafascial myxofibrosarcomas managed from 1/1/2000 to 1/1/2019 who received neoadjuvant or adjuvant radiation and had at least 2-years of oncologic follow-up at a tertiary referral cancer center. Our primary outcome was local recurrence. Comparisons were performed using Fisher’s Exact Test or Students t-test. A p-value < 0.05 was considered significant. Results: Fifty-three patients (18 VAC temporized, 35 single stage) were included. While VT patients were older (74.9 ± 10.2 vs. 63.9 ± 13.6, p = 0.003), treatment groups did not significantly differ with respect to comorbidity, tumor volume, stage and grade. VT patients had significantly fewer local recurrences (5.6% vs. 28.6% after SS, p = 0.048) and R1 resections that required an unplanned readmission for tumor bed re-excision (0% vs. 37.1% after SS, p = 0.002). VT required more total surgeries (2.8 ± 0.9 vs. 1.8 ± 0.9 for SS, p = 0.0002). Post-operative infectious and wound complications were equivalent (Table). Conclusions: Our VAC temporization strategy had a significantly lower LR than SS treatment. While high quality multi-institutional validation is required, VT may represent a paradigm shift in the management of myxofibrosarcoma.[Table: see text]
Does early palliative care reduce end-of-life hospital costs? A propensity-score matched, population-based, cohort study.
Authors: Seow Hsien , Sutradhar Rinku , Barbera Lisa Catherine , Guthrie Dawn , McGrail Kim , Burge Fred , Peacock Stuart , Chan Kelvin K.
Published: June 2021

12006

Background: Few studies describe how early versus late palliative care affects end-of-life health services costs. The aim of this study was to investigate the impact of early vs not-early palliative care among cancer decedents on the combined costs of receiving aggressive care (ED/hospitalization) and supportive care (home care/physician home visit). Methods: Using linked administrative databases, we created a retrospective cohort of cancer decedents between 2004 -2014 in Ontario, Canada. We identified those who received “early” palliative care (palliative care service used in the hospital or community 12 to 6 months before death [exposure]). We used propensity score matching to identify a control group of “not-early” palliative care, hard matched on age, sex, cancer type and stage. The propensity score included region, year, treatment, etc. We examined differences in median costs (including hospital, ED, physician, and home care costs) between pairs in the last month of life. Results: We identified 144,306 cancer decedents, of which 37% received early palliative care in the exposure period. After propensity score matching, we created 36,238 pairs of decedents who received early and not-early palliative care. After matching the early and not-early groups had equal distributions of age, sex, cancer type (24% lung cancer) and stage (25% stage 3 or 4). Among those who received early palliative care, 56.3% used hospital in-patient care in the last month, whereas 66.7% of the control group (not-early palliative care) used in-patient care; considering only inpatient hospital costs, those receiving early palliative care used a median of $2,894 in the last month of life compared to the control group of $5,311 (p < 0.001). Overall median costs in the last month of life for patients in the early palliative care vs the control group was $11,129 vs. $10,598 (p < 0.001). Conclusions: In our population-based, propensity-score matched, cohort study of cancer decedents, receiving early palliative care reduced the median overall health system costs, especially via avoiding hospitalizations in the last month of life.
The impact of advance care planning on hope among patients with advanced cancer.
Authors: Cohen Michael , Althouse Andrew , Chu Edward , Arnold Robert M. , White Douglas B. , Rosenzweig Margaret Q. , Bulls Hailey W. , Smith Kenneth , Schenker Yael
Published: June 2021

12029

Background: Providers often cite a fear of “giving up hope” as a reason they defer advance care planning (ACP) among patients with advanced cancer. We sought to determine whether engagement in ACP impacts patient’s hope. Methods: This is a secondary analysis of a randomized controlled trial of primary palliative care in advanced cancer. Patients who had not completed ACP at baseline were included in the analysis. ACP was assessed in the forms of an end of life conversation with one’s oncologist (EOL conversation) and completion of a living will/advance directive (AD). Measurements were obtained at baseline and 3 months. Hope was measured using the Herth Hope Index (HHI, range 12-48, higher scores indicate higher hope). ACP was measured with patient responses to a validated ACP questionnaire that queried (1) if they had had an EOL conversation with their provider and (2) if they had completed a living will or advance directive. Multivariate regression was performed to control for baseline HHI score, study randomization and age, religious importance, education, marital status, socioeconomic status, time since cancer diagnosis, pain/symptom burden (ESAS), and anxiety/depression score (HADS)—all variables known to be associated with ACP and/or hope. Results: A total of 672 patients with advanced cancer were enrolled in the overall study. The mean age was 69±10, and the most common cancer types were lung (36%), GI (20%) and breast/GYN (16%). In this group, 378 (56%) had not had an EOL conversation at baseline, of whom 29% (111/378) reported having an EOL conversation by 3 months. Hope was not different between patients who had or did not have an EOL conversation over the study period (ΔHHI 0.20 ± 5.32 vs -0.53 ± 3.80, p=0.136). After multivariable adjustment, hope was significantly increased in patients who had engaged in an EOL conversation (adjusted mean difference in ΔHHI 0.95 (95%CI 0.08-1.82), p=0.032). Similarly, of 216 (32%) patients without an AD at baseline, 31% (67/216) patients had subsequently completed one. Unadjusted hope was not different between those who had and had not completed an AD (ΔHHI 0.20 ± 3.89 vs -0.91 ± 4.50, p=0.085). After adjustment, hope was significantly higher in those who completed an AD (adjusted mean difference in ΔHHI 1.31 (95%CI 0.13-2.49), p=0.030), (Table). Conclusions: Our results demonstrate that hope is not decreased after engagement in ACP and may, in fact, be increased. These findings may provide reassurance to providers who are apprehensive about having these important and difficult conversations. Unadjusted and adjusted change in hope for those patients who had and had not had completed an EOL conversation or AD.[Table: see text]
Overall and progression-free survival in young breast cancer patients with low muscle mass and density.
Authors: Greiner Rebecca Sheaff , Flores Matthew , Boselli Danielle , Stone Taylor , Hadzikadic-Gusic Lejla , Hecksher Anna , Bailey-Dorton Chasse Margot , Wang Eric , Walsh Declan
Published: June 2021

12052

Background: Low muscle mass (skeletal muscle index, SMI) and density (skeletal muscle density, SMD) are associated with chemotherapy toxicity and shorter survival in women with breast cancer. This has not been studied specifically in women ≤ 40 years at diagnosis. They have different body compositions and more aggressive cancers than older women. We compared pre-treatment muscle measures in survivors and non-survivors and investigated their association with overall survival (OS) and progression-free survival (PFS). Methods: This case-control study included 112 women aged ≤ 40 years at diagnosis. Women with pre-treatment CT scans from 2009-2018 were identified; non-survivors were matched with survivors by age, year of diagnosis and disease characteristics. Body composition was determined by CT analysis. Measures were compared between the groups using Kruskal-Wallis tests. Kaplan-Meier methods summarized OS and PFS and the associations of muscle characteristics with OS and PFS were examined by univariate Cox proportional hazard models. Results: Median age was 35 years; median follow-up was 8.2 years. 75% had Stage II or III disease and 21% Stage IV disease. 33% were sarcopenic (SMI < 40) and 16% had low SMD (HU <37.8). Non-survivors had more intermuscular fat (IMAT), reduced SMD, and reduced skeletal muscle gauge (SMG). Sarcopenia was not associated with OS; however, sarcopenia was associated with shorter PFS. The median skeletal muscle gauge was 1973; low skeletal muscle gauge (SMG <1973) was associated with both shorter OS and PFS. Median IMAT was 1.6, and high IMAT (≥1.6) was associated with shorter OS and PFS. Conclusions: Low muscle mass (sarcopenia) at breast cancer diagnosis was associated with shorter PFS and low muscle density (low SMG and higher IMAT) was associated with shorter OS and PFS in women ≤ 40 years. These sub-optimal muscle characteristics may indicate an overall reduced state of health and/or decreased ability to tolerate treatment, thus reducing survival. Future research should determine the significance of muscle changes throughout treatment and establish standards for improved muscle health.[Table: see text]
Predictors of receiving survivorship care plans and visits.
Authors: Duffy Christine M. , Saiganesh Harish , Chrysanthopoulou Stavroula , Higel-Mcgovern Camille , Dizon Don S.
Published: June 2021

12055

Background: While the Commission on Cancer has eliminated strict quotas for accreditation, Survivorship Care Plans (SCPs) and/or Survivorship Care Visits (SCV) at treatment completion are encouraged. However, who receives a SCP or SCV, whether it impacts care, and impact of distress on care is unknown. We examined the provision of survivorship care at the Lifespan Cancer Institute (LCI) to determine (1) clinical and distress thermometer scores (DTS) association with SCPs and SCVs; (2) impact of SCV visits on specialty referrals, and (3) demographic and clinical predictors of receipt of SCP and SCV. Methods: We retrospectively reviewed EMR records on 1,960 patients at LCI between 2014-2017 for SCPs and SCVs and extracted demographics, treatment variables, and distress scores. We used T-test or Wilcoxon rank test and Chi-square tests for evaluating the bivariate associations of SCP and SCV with continuous and categorical factors respectively. We fit logistic regression models to assess the adjusted effect of these factors on receipt of SCP and SCV independently. All analyses were performed in R v4.0.2. Results: The mean age was 63.9 (SD=11.8), 67% were female, 51.2% were married or partnered. Breast (38.8%), lung (17.6%), and prostate (13.7%) were the most common cancers. DTS were recorded in 64% with mean of 3.88(SD=3.05): distress was higher in women (4.36, SD=3.01), breast cancer pts (4.53, SD=3.07), gyn (4.22, SD=3.07), pancreatic (4.12, SD=3.41) and anal cancers (4.52, SD=3.47) and in those with Stage IV disease (5.33, SD=3.43). SCPs were completed in 740 (37.8%) patients and of those 65.9% had a SCV. SCV were associated with more specialty referrals for psychiatry, physical therapy, nutrition, and sexual health but not smoking cessation or fiscal services. DTS were associated with increased referral to psychiatry only. The adjusted models (table) showed odds of receiving a SCP were higher in those younger, and having breast cancer v all other cancers, with prostate having lowest odds. For receipt of SCV, odds were higher in those younger, female, and having breast cancer, with prostate and lung having the lowest odds. Conclusions: Gender, age and type of cancer are significant predictors of receipt of SCP and SCV. SCP and SCV patterns may represent patient preferences, but practice patterns and unconscious biases may also play a part suggesting areas for further research and outreach.[Table: see text]
Multifactorial analysis of cancer patients’ willingness for COVID-19 vaccination.
Authors: Kosmidis Paris A. , Lagogianni Christie , Kosmidis Thanos
Published: June 2021

12062

Background: Public health authorities advocate vaccinations for the general population, including cancer patients and survivors. Since the onset of the COVID-19 pandemic, its vaccine has been eagerly awaited, but the extent of cancer patients’ willingness to get vaccinated is not clear. As health promotion is crucial for these individuals, it is important to measure and analyze their willingness to receive the vaccine. Methods: A few days after the regulatory approval for the first COVID-19 vaccine, the CareAcross online interactive platforms were used to evaluate the willingness of patients to get vaccinated. Through an online survey, within a few hours, 1106 cancer patients selected either “Yes, I plan to get the vaccine” or “No, I will not get the vaccine”. The patients were from the UK, Germany, France, Spain or Italy; they had been diagnosed with breast, lung, prostate or colorectal cancer. Their responses were analyzed to determine how their cancer diagnosis (including date, metastatic status, and other aspects), and their country of origin, affected their reported willingness to get vaccinated. Results: Overall, 70.6% of patients indicated willingness to get the vaccine (WTV), and 29.4% reported the opposite (NWTV). The strongest determinant of WTV was the patient’s country of origin: patients in the UK, Spain, Italy, Germany and France reported WTV of 84.1%, 64.2%, 58.7%, 47.4% and 38.3%, respectively. The next strongest determinant was the time elapsed since the patient’s diagnosis: for the largest population with available diagnosis date (451 UK patients), the average time since diagnosis for patients with WTV vs NWTV was: breast, 3.5 vs 2.5 years; lung, 1.6 vs 1.4 years; prostate, 2.4 vs 3.3 years; colorectal, 1.9 vs 1.5 years. Among patients from other countries with available diagnosis date: as the time since diagnosis increased, among 148 Italian patients WTV gradually increased; among 94 Spanish patients, WTV substantially decreased; among 85 French patients, WTV gradually decreased; among 50 German patients, WTV substantially increased. There was no significant correlation of WTV percentages with cancer type; metastatic status; triple negative vs non-triple negative among breast cancer patients; non-small cell vs small cell among lung cancer patients. Conclusions: Despite long-standing efforts of the scientific community for health promotion through the COVID-19 vaccine, a substantial percentage of cancer patients reported no willingness to get vaccinated. This appeared to depend on each patient’s country of origin, and the time elapsed since their diagnosis. This patient input was collected shortly after the first vaccine’s approval. With increasing evidence of efficacy and safety through more vaccinations of citizens and patients, willingness is expected to increase. We are in the process of conducting a follow-up survey to track these changes and update the results to be reportable during ASCO.
Treatment-specific risk of second malignancies in five-year survivors of diffuse large B-cell lymphoma.
Authors: Geurts Yvonne M. , Neppelenbroek Suzanne I.M. , So-Osman Cynthia , Vermaat Joost S.P. , van Spronsen Dick Johan , Plattel Wouter J. , de Weijer Roel J. , Verschueren Karijn M.S. , Zijlstra Josée M. , Koene Harry R. , Nijziel Marten R. , Schimmel Erik C. , Böhmer Lara H. , Ong Francisca , Visser Hein , van Kampen Daphne , Kersten Marie José , Aleman Berthe M.P. , Van Leeuwen Flora , Schaapveld Michael
Published: June 2021

12072

Background: Due to the historically less favorable prognosis of diffuse large B cell lymphoma (DLBCL), the burden of second malignant neoplasms (SMNs) has been rarely studied in DLBCL survivors. However, radiotherapy and chemotherapy may increase SMN risk among DLBCL patients. Anthracyclines may increase the risk of hematological malignancies, but it is not clear whether they also increase solid cancer risk. Methods: We established a multicenter cohort of 2,384 5-year DLBCL survivors treated at ages 15-60 years with radiotherapy and/or immuno-chemotherapy between 1989 and 2012. Observed numbers of SMNs were compared with expected cancer incidence in the general population to compute standardized incidence ratios (SIRs), absolute excess risks (AERs, per 10.000 person-years) and cumulative incidence. Treatment specific incidence was compared with general population rates and assessed within the cohort using Cox regression. Results: Most DLBCL patients received alkylating agents (95%), anthracycline-containing chemotherapy (95%) or radiotherapy (61%); 46% received rituximab. Median follow-up was 13.3 years; 17% of patients was followed ≥20 years. In total, 308 5-year survivors developed an invasive SMN (SIR 1.6; 95% confidence interval (CI), 1.4 to 1.8), translating into 56.2 excess cancers per 10.000 person-years (see Table for specific sites). In 20-year survivors of DLBCL, the SIR was 1.8 (95% CI 1.3-2.6). The 20-year cumulative incidence of any SMN was 18.7% (95% CI 16.5-21.0%). The SIR for any SMN was higher in patients <40 years at first treatment (SIR ≤40 years: 2.8, SIR >40 years: 1.4; p<0.001). Treatment specific results will be presented at ASCO21. Conclusions: DLBCL survivors experience higher risk of SMNs than the general population. Identification of patients at increased risk could improve follow-up care.[Table: see text]