bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical value of next-generation sequencing in endocrine therapy for advanced hormone receptor–positive/HER2-negative breast cancer.
Authors: Lv Dan , Liu Binliang , Lan Bo , Li Lixi , Sun Xiaoying , Ma Fei
Published: June 2022

1062

Background: Acquired gene mutation is a major mechanism of resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) facilitates the current assessment of the genomic profile in patients with advanced cancer. We performed this clinical trial to determine the landscape of gene mutation before endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. Methods: We conducted an open-label, single-center, multicohort, prospective study. Patients were women with pathologically and immunohistochemically confirmed HR-positive/HER-2-negative patients with advanced breast cancer. Patients relapsed during or after adjuvant endocrine therapy or progressed after completing at least one previous line of treatment for advanced breast cancer. Patients were assigned to four parallel treatment cohortsmatched to mutations identified in ctDNA: 1) cohort A comprised patients with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 2) cohort B comprised patients with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 3) cohort C comprised patients with HER2 mutations, preferred pyrotinib combined with endocrine therapy; 4) cohort D comprised patients with no significant gene mutation, making treatment plan according to the actual clinical situation. If more than one mutation was identified, the priority of entry is cohorts C, cohorts A and cohort B. In the A-D cohort, patients who obey the treatment plan are the compliance group, and patients who do not obey the treatment plan are the violation group. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS). Results: A total of 113 patients underwent NGS detection of ctDNA, and 84 patients were enrolled in the study. In all cohorts, combined median PFS was 4.9 months, and the median PFS in the compliance group was 3.0 months longer than in the violation group (6.03 vs 3.03 months, p = 0.0222, HR = 0.5743, 95%CI 0.3273-1.007). In cohort C, the median PFS was 11.1 months in the compliance group and 2.22 months in the violation group (p = 0.0067, HR = 0.1980, 95%CI 0.032-1.22). There was no significant difference in the median PFS between patients with and without compliance with the treatment protocol in cohort A and cohort B (p = 0.5054 and 0.7325, respectively). Conclusions: The study suggested that ctDNA detection may guide the optimal endocrine therapy strategy for patients with advanced breast cancer and achieve the benefit of progression free survival. NGS detection might distinguish patients with HER2 mutation and provide new treatment strategies. Clinical trial information: NCT03786575.
Real-world treatment patterns and outcomes among patients (pts) with second-line (2L) and third-line (3L) metastatic triple-negative breast cancer (mTNBC) in England using the Cancer Analysis System (CAS).
Authors: Chang Lawrence , Hall Peter S. , Preger Luciana , Sjekloca Nikoleta , Bergamaco Estevan , Broe Anne , Petrova Plamena , Berg Paul , Reich Adam , Pawar Neha , Gharaibeh Mahdi
Published: June 2022

1075

Background: TNBC is the most aggressive type of breast cancer due to rapid growth, metastasis, and recurrence post-treatment. This study aimed to assess real-world treatment patterns and survival of pts with mTNBC who received 2L and 3L therapy in England and report OS and PFS of pts receiving 2L therapies stratified by treatment-free interval from the curative setting. Methods: This retrospective study using the CAS database, included pts with mTNBC who received at least three systemic treatments (at least two in metastatic setting) for TNBC during the years 2012 to 2020. Cohort2L included pts with initial early-stage BC diagnosis and treatment (at least two systemic treatments prior to 2L). Cohort3L included pts initially diagnosed with either early-stage TNBC, or de novo advanced TNBC (at least two systemic treatments prior to 3L). The two cohorts are not mutually exclusive. The study outcomes were stratified by cohort (Cohort2L and Cohort3L) and treatment-free interval (<12 m versus ≥12 m from end of curative treatment to start of 1L treatment, Cohort2L only). Kaplan-Meier methods estimated progression-free survival (PFS) and overall survival (OS). PFS was proxied by ‘Time to treatment discontinuation or death’ (TTDD). Log-rank tests compared the distribution of OS and PFS for 2L stratified by treatment-free interval (<12 m versus ≥12 m). Results: Cohort2L included 606 pts and Cohort3L included 374 pts. Tumor morphology was similar across Cohorts. Pts at 3L had worse ECOG performance score compared to 2L, and more pts with de novo advanced TNBC had brain metastasis at any point after diagnosis than pts diagnosed with early-stage TNBC. Regimens at 2L for Cohort2L included capecitabine (32%), eribulin (16%), carboplatin and gemcitabine in combination (12%), and paclitaxel (10%). A similar distribution was seen for Cohort3L. Regimens at 3L (Cohort3L only), included eribulin (38%), capecitabine (16%), and paclitaxel (13%). Stratifying Cohort2L by treatment-free interval did not exhibit significant differences in PFS nor OS by log rank tests (Table). Conclusions: This nationwide study, in England, accentuates the significant unmet need in 2L and 3L therapy for mTNBC highlighted by the poor prognosis. The stratification by prior treatment-free interval from curative setting did not show a difference in OS or PFS for patients receiving 2L treatment. [Table: see text]
Comprehensive whole-exome and transcriptome profiling to identify actionable alterations associated with response to PARP inhibitors in breast cancer.
Authors: Dombrowski Susan M. , Udhane Sameer S. , Basu Gargi D. , Hall David W. , Hoag Jess W. , Alyaqoub Fadel S. , Noel Pawan , Szelinger Szabolcs , Wang Min , Ozols Audrey A. , LoBello Janine R. , Thakkar Snehal Govind , Baehner Frederick L. , O'Shaughnessy Joyce
Published: June 2022

1096

Background: The use of targeted therapies identified using genetic and genomic approaches is now routine in breast cancer (BC). In this clinical lab experience study the frequency of actionable somatic alterations in DNA repair pathway genes associated with the use of PARP inhibitors (PARPi) is described. Methods: BC samples were sequenced with the Oncomap ExTra assay, which uses whole-exome DNA sequencing with germline subtraction to detect somatic single base substitutions, indels, and copy number alterations, and RNA sequencing to detect gene fusions. Clinically actionable alterations were defined as associated with FDA approved drugs or clinical trial enrollment. Here, the focus is on 49 repair genes associated with PARPi response: ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, EPCAM, ERCC1/2/3/4/5, FANCA/C/D2/E/F/G/I/L/M, MLH1, MRE11A, MSH2/6, MUTYH, NBN, PALB2, PMS2, PPP2R2A, PTEN, RAD21/50/51/51B/51C/51D/52/54L, XRCC1/2/3. Results: Of 1103 BCs, 246 (22.3%) had mutations in repair genes; 69 (6.3%) were in BRCA1/2. Repair gene mutations were less common in HER2+ cancers (n=27, 14.3%) compared to HR+ HER2- (n=156, 23.9%) or TN cancers (n=49, 26.1%) (p<0.01). Across subtypes, the top four most commonly mutated of the repair genes were PTEN (27.2%), ARID1A (22.8%), BRCA2 (14.2%), and BRCA1 (14.2%); 33 cancers (13.4%) had mutations in multiple (≥2) repair genes. For the 69 cancers with BRCA1/2 mutations, 11 (15.9%) carried other repair gene mutations (9 of 35 BRCA1; 3 of 35 BRCA2). RNA sequencing found 19 fusions in repair genes in 17 patients (1.5%); CDK12 was involved in 13 (68.4%), and RAD51C in 3 (15.8%). Fusion incidence was more frequent in HER2+ cancers (p<0.01) (Table). Conclusions: PARPi therapy is FDA approved for HER2- germline BRCA1/2 mutated BC patients. Recent evidence suggests somatic BRCA1/2 mutations predict PARPi benefit (Tung, NM. J Clin Oncol 2020). In addition to BRCA1/2 alterations, our study also highlights the importance of alterations in other DNA repair genes associated with response to PARPi. Trials are ongoing to determine if these genes predict for PARPi benefit.[Table: see text]
A collaborative model for continuing medical education: Impact of a distance learning curriculum for existing radiation oncology centers in Africa and Latin America.
Authors: Balbach Meridith Leigh , Neely Grantly , Yorke Afua Adutwumwaa , Medina Evangelina Figueroa , Paly Jonathan Judd , Shulman Rebecca Maria , Cutrer William B. , Benjamin Li
Published: June 2022

11007

Background: We aimed to evaluate the outcomes and generalizability of a distance learning curriculum on intensity modulated radiotherapy (IMRT), a course developed for radiotherapy clinics across Africa and Latin America (LATAM) at no cost, as measured by a knowledge-based multiple-choice exam, learner self-evaluation, and open-ended feedback. Methods: Following needs identification studies, a curriculum entitled “IMRT 2.0” was created for an audience that included medical physicists, radiation oncologists, radiation therapists, and trainees. Volunteer educators delivered 27 hour-long sessions 1-2 times weekly for four months using video conferencing to African and LATAM programs in English and Spanish, respectively. Recordings and educational materials were shared following each session. Pre- and post-course multiple choice examinations were administered to LATAM participants, and pre- and post-course Likert scale self-evaluation and open-ended feedback were collected for both programs. Paired sample t-tests and chi-squared tests were performed for all available paired quantitative and categorical data, respectively. Pearson correlation coefficient, multivariate linear regression, and spline regression models were used to explore impact of course attendance on outcomes. Results: 25 centers across Africa (12 + 1 sister institution in Pakistan) and LATAM (12) were recruited, the majority (92%) of which were recently transitioning or planning to transition to IMRT, yielding a total of 332 enrolled participants. 27 sessions were delivered with a mean of 44 (std dev 22.5) and 85 (std dev 25.4) participants per session for the African and LATAM programs, respectively. Paired pre- and post-course data demonstrated significant improvement in both knowledge (n = 51, p <.001) and overall self-confidence (n = 85, p <.001). Synchronous participation did not predict greater score improvement or increase in self-confidence. Thematic analysis suggests that participants found great value in this course and look forward to future learning. Conclusions: A volunteer-driven course on IMRT is generalizable across regions in different languages and serves as an effective hub to arm participating centers with the knowledge and confidence they need to enhance patient care at their institutions. This benefit may propagate as participants become the next generation of trainers. Other fields and specialties aiming to reduce global health care disparities through training efforts could consider adopting this approach.
Implementation and efficacy of a fellow-led, case-based noon lecture series.
Authors: Dickerson James , Myall Nathaniel James , Roy Mohana , Johnson Tyler Paul
Published: June 2022

11011

Background: For new fellows, learning clinical oncology represents an enormous challenge. Few data support specific didactic approaches. The senior author (TPJ) developed a novel curriculum, emphasizing deliberate practice as part of a design grounded in Ericsson’s “expert performance approach”. These noon conferences are case based with a focus on key clinical trials and NCCN guidelines. In comparison to didactics given directly by faculty, these conferences are primarily presented by a senior teaching fellow with an invited faculty member adding additional commentary as an “expert discussant”. We surveyed fellows to assess perception of efficacy and also created a board style test to evaluate knowledge gains. Methods: The curriculum began in 2020. After one year, we surveyed fellows with a five-point likert scale survey to quantify their perception of the curriculum. In 2022, we created a pair of 18-question lung cancer specific board style tests for the five teaching sessions on lung cancer. Prior to the first conference, the pre-test was sent to fellows electronically; after the final lecture the other 18-question test was sent out. Differences in the overall cohort’s test score were examined via a paired student t-test. Results: On the 2021 survey, 59% of fellows responded (17 of 29). Of the respondents, 83% attended at least half of the lectures (14 of 17). When asked to compare this conference series to traditional lecture-based series, 59% (10 of 17) agreed with the statement that "this series is one of the very best I've encountered" and all said it was at least “better than average.” 94% of respondents (16 of 17) said the series equipped them for clinical practice to either a “significant” or “remarkable” degree. 94% of respondents (16 of 17) agreed the conferences helped them learn to “think like oncologists.” For the five session lung cancer block, fellows reported attending an average of 3.6 ± 1.4 sessions (n = 13). On the 18-question pre-test (n = 19), the average score ± one standard deviation was 73% ± 15%. For the post-test (n = 13), the average was 68% ± 17% (p = 0.48). Conclusions: We developed a novel curriculum to replace traditional didactics. Fellows perceived the curriculum to be exceptionally strong as compared to traditional lecture series, felt it prepared them well for practice, and said it taught them to think like oncologists. Pre/post knowledge assessments did not show an improvement in knowledge. Distribution to larger numbers of fellows–especially early learners–may better power a study to detect improvements in learning.
Factors associated with altmetric attention scores for randomized phase III cancer clinical trials.
Authors: Rooney Michael Kevin , Ludmir Ethan B. , Fuller Clifton Dave , Warner Jeremy Lyle
Published: June 2022

11014

Background: The rise of the internet and social media has created new opportunities for the rapid sharing of scientific findings among professional and public communities. Altmetric Attention Scores (Altmetrics) are real-time measures of scientific impact and attention through various public outlets, including news, blogs, and social media. Distributions and patterns of Almetrics for high-impact clinical cancer research remain under-reported. Our goal was to describe the relationship between Altmetrics and other characteristics of published trials. Methods: We identified all two-arm superiority phase III cancer randomized controlled trials (RCTs) with a publication date between 2015-2020 from HemOnc.org. For included trials, we tabulated the followed the data: Altmetric score as of February 11, 2022; positive study (yes/no); FDA registration trial (yes/no); primary endpoint (categorized as overall survival (OS), progression-free survival (PFS), event-free/disease-free survival (EFS/DFS), or other); journal tier (defined as tier 1: NEJM, Lancet, JAMA; tier 2: JCO, Blood, Lancet Oncology, JAMA Oncology, Annals of Oncology or Tier 3: other). Univariable testing was performed with Pearson correlation, Wilcoxon rank sum, and Kruskal-Wallis testing to identify associations between predictor variables and Altmetrics. For factors with significant univariable associations, we generated a multiple linear regression model to identify clinical trial factors predictive of Altmetric attention scores, with alpha = 0.05 defining statistical significance. Results: Of 673 publications identified per inclusion/exclusion criteria, Altmetric scores were found for 638 (95%). The median score was 38.9 (IQR 12.4-126.7) – well above the 95th percentile for all Altmetric scores. On univariable testing, positive studies (P < 0.001), registration trials (P < 0.001), those published in tier 1 journals (P < 0.001), and trials with primary endpoint of OS (P = 0.002) were associated with increased Altmetric scores. On multivariable testing, positive studies (P = 0.006), registration trials (P < 0.001), studies published tier 1 journals (P < 0.001), and those reporting on OS (P = 0.03) persisted as significantly associated with increased engagement as measured by Altmetric scores. Conclusions: Social media and other online platforms represent an increasingly important avenue for the sharing of scientific and medical research. In this cross-sectional observational study, we found that certain characteristics of cancer clinical trials and publications are predictive of impact as measured by Altmetric scores. Specifically, positive registration trials published in traditionally defined high-impact journals and those reporting on OS as a primary endpoint tend to have the greatest Altmetric attention scores. The significance and consequences of these relationships warrant further investigation.
Impact of structured debriefing sessions on residents rotating on inpatient oncology.
Authors: Dalal Hina , Thilges Sarah , Mumby Patricia B. , Chervinko Nazzara , Girardi Ellen , Lo Shelly S.
Published: June 2022

11018

Background: Participating in end-of-life (EOL) care may lead to physician distress and burnout. Residents rotating on inpatient oncology services often care for patients and families nearing the EOL. There is no standardized resident training for EOL care nor are there standardized methods to assist with resultant emotional distress. Studies have demonstrated that residents on hematology/oncology rotations experience acute empathy decline, which can lead to cynicism and depersonalization, contributing to burnout (McFarland, 2016). Our objective was to prospectively evaluate the impact of a structured debriefing session during a 4-week inpatient oncology rotation on residents' concerns about death and rotation satisfaction. Methods: During week 1, residents completed a 10-item Concerns about Dying (CAD) instrument (Mozer, 2004). During week 3, residents participated in a structured 60-minute debriefing session with a clinical psychologist or licensed social worker specializing in hematology-oncology. During week 4, residents completed the CAD and an end-of-rotation self-assessment. Results: 58 individual residents rotated through inpatient oncology at Loyola University Medical Center from 7/2020 – 1/2022. 15 residents were excluded as they did not complete both the pre and post surveys. Trainees had a lower CAD score at the end of their oncology rotation, indicating a more positive attitude towards death and dying. PGY1s had the greatest decrease in CAD score over 4 weeks. Anxiety (70%), relief (70%), satisfaction/pride (63%) and sadness (58%) were the most common emotions residents felt while providing EOL care. 42/43 (98%) residents were comfortable discussing EOL topics with a licensed counselor and 40/43 (93%) felt the debriefing had a positive impact on their rotation. 38/43 residents (88%) believed the debriefing reduced sentiments of cynicism and dissatisfaction caused by emotional distress related to EOL care. Conclusions: Resident concerns about death decreased during a 4-week inpatient oncology rotation in which a structured debriefing program occurred during week 3. Although the study protocol does not provide causation, it suggests the debriefing allowed residents to reflect on EOL care and enhance their ability to cope with distress. The favorable feedback from this pilot led to a permanent curricular change for the inpatient oncology rotation. Strategies to assess and manage emotional strain among residents providing EOL care remain limited and warrant further investigation.[Table: see text]
Piloting virtual mentorship: Evaluating acceptability and influence on wellness and professional identity in medical oncology (MO).
Authors: Fung Andrea S. , Nowell Lorelli , Afzal Arfan R. , Thiessen Maclean Harvey , Campbell Alexi , Hao Desiree
Published: June 2022

11022

Background: Despite extensive literature on the value of mentorship in academic medicine, little evidence exists to inform mentorship practices in MO. In 2021, the Canadian Association of Medical Oncologists (CAMO) piloted a national, 6-month virtual mentorship program consisting of 2 group mentoring events and additional 1-on-1 mentoring activities, to better support the needs of MO trainees. Feedback was obtained from participants to gain insight into how virtual mentorship might impact physician wellness and formation of professional identity, and to inform future iterations of CAMO’s virtual mentorship strategy. Methods: All Canadian MO residents/fellows were invited to participate in the program. Electronic surveys were completed by participants at baseline, after each group event, and at program completion. Surveys evaluated the program content and format, and used validated questionnaires for evaluating physician wellness/burnout (Stanford Professional Fulfillment Index [SPFI]), and professional identity (Macleod Clark Professional Identity Scale [MCPIS]). Cohort characteristics and survey responses were summarized using descriptive statistics. Procedures for survey data collection and analysis were ethics approved. Results: At baseline, respondents (n = 38) were predominantly female (63%), and < 35 years (76%). 50% were married. On average, 78% of respondents ranked the virtual group mentoring events as meeting expectations. Program strengths identified by participants included meeting mentors outside of their own centre, meeting other trainees from across the country, and learning more about work-life balance/physician wellness. The main critique was insufficient time for interaction. Of the 34 MCPIS respondents, 94% were pleased to belong to the profession of MO, 91% identified positively with members of their profession and 77% felt like a member of the profession themselves. The average score on the SPFI scale was 2.73±0.71 (n = 34). Although 85% of respondents found their work meaningful, 71% satisfying, and 50% felt they were contributing professionally in valued ways, only 38% met criteria for professional fulfilment (score ≥3.00). 27% met criteria for burnout (score ≥1.33), 15% found their work physically exhausting and 9% found their work emotionally exhausting. Conclusions: CAMO’s pilot virtual mentorship program highlights that technology can be successfully leveraged to facilitate mentoring. The majority of MO trainees identified positively with their profession, yet only 38% reached the threshold for professional fulfillment and nearly a third met criteria for burnout. Longitudinal follow-up among mentored trainees is needed to provide insight into whether mentorship may influence physician wellness and professional identity over time.
A needs assessment survey to inform a general practitioner in oncology (GPO) training program in Nepal.
Authors: Gyawali Bishal , Carson Laura M. , Thapa Niresh , Savage Colleen , Rawal Mangal , Berry Scott R. , Poudyal Bishesh Sharma
Published: June 2022

11024

Background: Nepal is a low-income country with a population of over 30 million that faces a significant burden of cancer, with approximately 60,000 patients receiving a cancer diagnosis per year. However, a lack of cancer care providers is recognized as a major barrier to cancer care in Nepal. To address this gap, a national GPO training program may be an effective task-shifting strategy to increase the oncology workforce. A needs assessment survey was conducted to determine baseline oncology training for Nepalese General Practitioners (GPs) and the feasibility and desirability of establishing a GPO training program in Nepal. Methods: A survey was distributed to 171 GPs in Nepal. The survey was distributed via the REDCap electronic database, a secure-web-based software platform based at Queen’s University in Kingston, Ontario, Canada. Reminders were sent out via social media accounts. The survey results were recorded anonymously from February to July 2021. Results: Data was collected from 71 GPs in Nepal. Data revealed significant gaps in oncology training, with only 6% of respondents reporting undergoing a mandatory oncology rotation during their training, and 15% indicating their training adequately prepared them to care for patients with cancer. Although respondents reported seeing an average of 1-5 cancer patients per day, only 9% reported providing chemotherapy treatment, and 36% indicated regular provision of follow-up cancer care. Only 1 in 5 general practitioners reported having radiation oncology services available at their institution or an institution within the same zone. 96% of GPs surveyed agreed that there is a need for a GPO program, and 71% reported they would be very interested in participating in this type of training. A majority of respondents indicated a preference for self-directed and small-group learning as the preferred modes of content delivery in a GPO training program. Conclusions: Our findings indicate a need and high level of desirability for a national GPO training program in Nepal. Further, the needs assessment provides insight into practitioner perspectives on information needs and content delivery. This data will be used to guide future curriculum development for the Nepal GPO program. [Table: see text]
Gaps in adolescent and young adult oncology education during medical and pediatric hematology/oncology fellowship training.
Authors: Duvall Adam , Moerdler Scott , Freyer David R. , Grimes Allison , Hayes-Lattin Brandon M. , Monga Varun , Prasad Pinki Kumari , Roth Michael
Published: June 2022

11026

Background: There are limited data on the extent of adolescent and young adult (AYA) education in pediatric and medical oncology fellowship programs. The purpose of this study was to assess the prevalence and content of AYA-focused training during pediatric and medical oncology fellowship and identify knowledge gaps for targeted educational curricular development. Methods: An anonymous, web-based survey for educators and trainees was developed, piloted and optimized by a study team comprising pediatric and adult oncologists. The survey contained questions on respondent demographics, AYA curriculum, provider comfort in managing specific AYA care domains, and priorities for future AYA educational content. In October 2021, email invitations containing the survey link were sent to program directors (PDs) and associate program directors (APDs) at 251 hematology/oncology fellowship programs (with 119 pediatric and 178 adult PDs/APDs) identified through the American Medical Association’s Fellowship and Residency Electronic Interactive Database Access. PDs were asked to participate and also distribute the survey to current fellows. The survey remained open for 3 months. Fisher’s exact test was used to assess for associations between discrete variables including amount of current education vs level of importance and demographic groups. Results: Respondents represented 69 programs (27%). There were 130 respondents who completed curriculum and demographic questions and 112 who completed detailed topic questions. Respondents comprised 51 PDs/APDs (32 pediatric and 19 adult) and 58 fellows (33 pediatric and 25 adult). 85% of PDs (44/51) do not have a formal AYA curriculum. Of these, 80% (35/44) offer some topic-specific lectures, while 20% (9/44) provide little/no education in any topics. For nearly all topics, at least 45% of respondents reported little/no education. Although onco-fertility and survivorship are the most frequently taught topics, 36% and 42% of respondents, respectively, reported little/no education in these areas. Substance abuse is least commonly taught. Both PDs and fellows believe that AYA topics are more important for inclusion in future curricula despite how infrequently they are currently taught (very/extremely important for inclusion vs moderate/great deal of current amount of education, p = 0.0001 for all topics). Overall, respondents indicated the most important topics for inclusion in fellowship curriculum were onco-fertility (82%), survivorship (78%), and communication (77%). Conclusions: These data highlight the large gap in hematology/oncology fellowship education in AYA topics and a paucity of formal educational curricula. Efforts are needed to provide both medical and pediatric oncology fellows with the knowledge and skills required to provide optimal care for AYAs.
Patient-reported outcomes for measuring the quality of life in advanced breast cancer treated with third-line and beyond chemotherapy-based regimens: A national cross-sectional study.
Authors: Guan Xiuwen , Yan Xiaoyan , Wang Ying , Hu Xichun , Sun Xiaoying , Chen Zhanhong , Zhang Xiaochen , Dong Ying , Chen Wenyan , Shi Yanxia , Cheng Jing , Mei Zhihong , Ma Fei
Published: June 2022

1103

Background: Prolongation of survival and maintenance of quality of life (QoL) are the primary therapeutic goals in advanced breast cancer. Around 10% of adverse events (AEs) in the CTCAE are symptomatic AEs (e.g., nausea, sensory neuropathy), which can severely and directly affect the QoL of patients. However, seldom evidence mapped the QoL and symptomatic AEs utilizing patient-reported outcomes (PROs) in heavily pretreated breast cancer patients. This study aimed to investigate the PROs for measuring the QoL and symptomatic AEs of advanced breast cancer treated with third-line and beyond chemotherapy-based regimens in China. Methods: This national survey enrolled patients with advanced breast cancer receiving third-line and beyond chemotherapy-based regimens in 59 centers all over China from March to April in 2021. Each patient filled out a questionnaire containing demographic information, medical history, EORTC-QLQ-C30, and symptomatic AEs. The symptomatic AEs included fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, alopecia, fever, and limb numbness. The range method was used for the linear conversion of the PRO scores, which were converted into standardized scores of 0 to 100. Results: This study enrolled 1015 patients with the median age of 52 years. The QoL of all patients were poor, with the global health status score of 52.4±17.7 (Table). All the symptomatic AE scores were low among the patients. However, no significant differences were observed in global health status and symptomatic AEs between mono-chemotherapy and multi-agent chemotherapy (All P>0.05). Conclusions: The QoL of advanced breast cancer patients treated with third-line and beyond chemotherapy were poor, especially in symptomatic AEs. In addition, the EOTRC-QLQ-C30 scale appears to underestimate the differences in symptomatic AEs between mono-chemotherapy and multi-agent chemotherapy, probably due to a lack of sensitivity of the scale, which fails to match the actual clinical observations of the PROs and QoL. Therefore, new scales need to be developed for the evaluation of symptomatic AEs and QoL in advanced breast cancer. [Table: see text]
Are we doing it right? Mentorship challenges for oncology fellows and early-career faculty from backgrounds underrepresented in medicine.
Authors: Idossa Dame , Velazquez Manana Ana I. , Horiguchi Miki , Alberth Julia , Abuali Inas , Smith-Graziani Demetria Joy , Lopes Gilberto , Lubner Sam Joseph , Duma Narjust
Published: June 2022

11047

Background: Physician workforce diversity can be a driver of institutional excellence, improving innovation and reducing health disparities. The current diversity of the hematology/oncology (HO) workforce does not reflect that of the US population. The role of mentorship in increasing HO fellows’ interest in pursuing careers in HO has been described previously. However, the mentorship experiences of fellows and early career faculty from backgrounds underrepresented in medicine (UIM) in HO has not been fully characterized. Therefore, we compared the mentorship experiences of UIM and non-UIM trainees and early career faculty in HO subspecialties. Methods: We conducted cross-sectional online survey of HO subspecialists including current fellows and faculty within 5 years of end of training. The anonymous survey was distributed via email and social media channels in April 2020. Fisher’s exact test and multivariable logistic regression models were used to conduct comparisons between study groups. Results: Of the 306 respondents, 64 (21%) were UIM and 161 (53%) identified as male. UIM participants were less likely to have a primary mentor (66%) than non-UIM participants (80%, p = 0.015). Among those who had a primary mentor, UIMs were more likely to meet infrequently (greater than every 3 months, p = 0.007). Furthermore, UIMs were more likely to report having mentors outside their own institution (47% vs 40% non-UIM, p = 0.002) and making compromises to gain access to mentorship (36% vs 23% non-UIM, p = < 0.001). In addition, UIM participants were less likely to have an advisor (38% vs 54% non-UIM, p = 0.017), a coach (13% vs 20% non-UIM, p = 0.054), or a sponsor (19% vs 26% non-UIM, p = 0.046). UIMs were also less likely to apply for grants (34% vs 42% non-UIM, p = 0.035) and awards (28% vs 43%, non-UIM p = 0.019). In multivariable models, UIM individuals were more likely to make compromises to gain access to mentors (OR = 1.96, p = 0.047) and this remained significant for females (OR = 2.17, p = 0.005). Lastly, US born individuals had higher odds of having a primary mentor than non-US-born individuals (OR = 2.43, p = 0.004). Conclusions: In the largest study to date characterizing the mentorship experience of HO trainees and junior faculty, we found that UIM individuals were significantly less likely to find effective mentorship and were less likely to apply for awards and grant support. Understanding the challenges of UIM trainees can help shape training environments in academic medicine to ensure these are grounded in diversity and inclusion. Given the importance of workforce diversity, training programs in HO must consider structured programs and other innovations to improve mentoring experiences of UIM trainees and junior faculty.
Comparison of methodology in the collection of gender and race/ethnicity in hematology and oncology journal editorial boards.
Authors: Patel Shruti Rajesh , Riano Ivy , Abuali Inas , Ai Angela , Geiger Gabriella , Pimienta Jacqueline , Ramirez Roggio Adriana C. , Dhawan Natasha , Salinas Alexandra Lizette , Duma Narjust , Dizman Nazli
Published: June 2022

11061

Background: Reporting on disparities is strongly influenced by the methodology used to collect race/ethnicity and gender data. Incorporating gender and race into research has its challenges, as these variables are difficult to define. As underrepresentation of minorities and women continues to persist in many facets of academia, it is important to assess the accuracy of differing methodologies. While asking individuals to self-identify their race and gender remains the gold standard of reporting, low response rates and response bias have been shown to affect results. In our initial study on representation in editorial boards, gender and race/ethnicity were determined based on publicly available data which can lead to misclassification of editors. We aimed to add to our study by asking editors to self-report their gender and race in hopes to validate our methodology given the importance of considering gender and race in academia. Methods: Of the 60 highest impact journals in oncology, hematology, radiation oncology, and surgical oncology identified, race/ethnicity and gender determinations were made using two methods. All senior editors were sent a survey via email asking participants to self-report their gender, race/ethnicity, age, and job characteristics. Gender and race were also assigned to the editors by a diverse coding team based on publicly available data and the NIH's OMB Directive 15 as a framework. The self-reported data was then compared to data that was assigned by our team. Results: 66 of the 793 (8.3%) editorial board members included in the study responded to the survey. Of the 66 respondents, gender was assigned correctly 100% (66/66) of the time and race was assigned correctly 95.5% (63/66) of the time. Of the 66 respondents to the self-survey of the 793 editorial board members surveyed. A significantly lower proportion of men responded to the survey compared to the gender breakdown of the 793 editorial board members (54.5% vs 72.6%; p = 0.000279). The three incorrectly identified respondents self-identified as Native Hawaiian, White, and Middle Eastern. Conclusions: Multiple recent reports have demonstrated high rates of sexual harassment, gender bias, and exclusion in the field of oncology. Collecting data on racial/ethnic groups and gender is imperative to understand the academic landscape of oncology and work towards a more equitable environment. Notably, this data from our study supports the methodology of a diverse coding team assigning gender and race based on publicly available data and the NIH's OMB Directive 15 as a framework as an alternative to self-report. Our study also demonstrates the low response rates and significant discrepancies in the demographic of respondents seen in survey-based identification.
Interim analysis of a phase I study of SNK01 (Autologous Nongenetically Modified Natural Killer Cells with Enhanced Cytotoxicity) and avelumab in advanced refractory sarcoma.
Authors: Chawla Sant P. , Chua-Alcala Victoria S. , Gordon Erlinda Maria , Kim Ted T. , Feske William , Gibson Brenda L. , Chang Paul Y , Robinson Debra , Song Paul Y.
Published: June 2022

11517

Background: For patients (pts) with advanced sarcomas in the relapsed/refractory setting, there are very few if any effective salvage treatment options. The likelihood of response and/or tumor control only diminishes with each subsequent line of therapy. Monotherapy of PD-L1 inhibitors has shown modest to no activity in most sarcomas, especially in tumors that have little to no PD-L1 expression. Natural killer (NK) cells have recently been implicated in the antitumor response to immune checkpoint inhibitors with some evidence suggesting a role in PD-L1 negative tumors. SNK01 is a first-in-kind, autologous nongenetically modified NK cell therapy with highly enhanced cytotoxicity and over 90% activating receptor expression which can be consistently produced from heavily pretreated pts. Avelumab is an anti-PD-L1 immunotherapy with dual engagement of both the adaptive and innate immune systems. We hypothesized that this combination would be safe, and together better overcome the immunosuppressive tumor microenvironment. Methods: In this Phase I study (NCT03941262), cohort 4 is comprised of up to 18 pts treated with 800 mg of avelumab + 4 x 109 SNK01 cells every two weeks via IV Infusion. Pts were eligible regardless of PD-L1 status and permitted to continue treatment indefinitely until progression or unacceptable toxicity. The primary endpoint is safety. The secondary endpoints include overall response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: As of February 1, 2022, 15 pts with advanced refractory sarcoma have been enrolled. Median age is 50 (range 20-75) and 8 were male. Pts had a median of 5 lines of prior therapy (range 1-8). The subtypes included 6 leiomyosarcoma, 2 osteosarcoma, 1 pleomorphic liposarcoma, 1 Ewing’s sarcoma, 1 epithelioid sarcoma, 1 epithelioid mesothelioma, 1 endometrial stromal sarcoma, and 1 sarcoma NOS. There were three Grade 2 or 3 adverse events related to avelumab, but unrelated to SNK01. Best objective response by RECIST 1.1 was PR in 2 pts (ORR of 13.3%) and SD in 3 pts. Median PFS is 11.14 weeks. Several pts had PD-L1 negative disease and response appears to be independent of PD-L1 status. Of pts who progressed in this cohort, several reported an overall improvement in their QoL and some pts became eligible to be treated with additional salvage chemotherapy, resulting in some additional clinical response. Conclusions: SNK01 combined with avelumab was safe and well tolerated and appears to have some clinical activity against several types of heavily pretreated advanced sarcoma, independent of PD-L1 status. It may also keep rapidly progressing disease stable enough to allow additional cytotoxic chemotherapy. A proposed study expansion is planned. Clinical trial information: NCT03941262.
Phase I study of pegylated liposomal doxorubicin in combination with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory sarcoma and other malignant solid tumors.
Authors: Lu Suying , Wang Juan , Huang Junting , Sun Feifei , Zhu Jia , Zhen Zijun , Li Hui , Sun Xiaofei , Zhang Yizhuo
Published: June 2022

11519

Background: Pegylated liposomal doxorubicin (PLD) was found to have improved toxicity profile, especially with regards to reduced cardiotoxicity. The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of PLD in combination with cyclophosphamide and vincristine (PCV regimen) and describe the toxicities and response of this regimen. Methods: This was an open-label, single-center, single-arm phase I study utilizing a “3 + 3” design. The primary endpoint was the MTD of PLD, and the secondary endpoints included safety, objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Efficacy was evaluated using RECIST 1.1. PFS was defined as the time from treatment until disease progression or death. This study included cohort A and cohort B. Three dose levels were studied in cohort A, PLD 30 mg/m2 (L1), 40 mg/m2 (L2) or 50 mg/m2 (L3) d1 + cyclophosphamide and mesna at 1 g/m2/d d1-2 + vincristine 1.5 mg/m2/d (≯2mg) d1 every 3 weeks. As the endpoint of the study could not be reached, we changed the dose of cyclophosphamide and mesna to 1.5 g/m2/d d1 in cohort B. Results: Eleven in cohort A and 34 in cohort B were enrolled, the median age was 6 years (range 1-15). Forty-three patients were eligible and evaluable for toxicity, and 35 (77.8%) patients were evaluable for response. Diagnoses were rhabdomyosarcoma (n = 29, 64.4%), Ewing's sarcoma (n = 4), and others. The median number of prior regimens was 2 (range 1-5). The most common adverse event (AE) was grade 3 or grade 4 neutropenia with a proportion of 90.9% and 65.5% in cohort A and cohort B, respectively. There was no significant difference in ORR (60% vs. 48%) and DCR (90% vs. 88%) between the two cohorts. The ORR (60% vs. 0, P = 0.019) and DCR (96.7% vs. 40%, P = 0.006) were significantly higher in Group 1 (rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumor, fibrosarcoma, undifferentiated sarcoma) compared with Group 2 (neuroblastoma, osteosarcoma, embryonal sarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor). The 12-month PFS of Group 1 was also better than Group 2 (79% vs. 60%, P = 0.041). Conclusions: The PCV regimen demonstrated an acceptable toxicity profile and promising clinical efficacy in pediatric patients with R/R rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumor, fibrosarcoma, and undifferentiated sarcoma. Increasing the dose of cyclophosphamide did not improve the efficacy, but increased the toxicity. The RP2D for future studies is PLD 30 mg/m2/d for one day. Clinical trial information: NCT04213612. [Table: see text]
The efficiency of anlotinib in osteosarcoma with chemoresistance: Exploratory therapy based on PDX models and next-generation sequencing.
Authors: Long Zuoyao , Fu Zhanli , Yunus Aikebaier , Lu Yajie , Li Minghui , Chen Guojing , Li Jing , Zhang Hong-Mei , Wang Zhen
Published: June 2022

11527

Background: It’s urgent to find a new approach for the treatment of progressed osteosarcoma in neoadjuvant chemotherapy. Using patient-derived xenograft (PDX) models and next-generation sequencing (NGS), we have explored the efficiency of anlotinib in these patients. Methods: Frozen osteosarcoma tissues were used to establish PDX models. Ten samples of each PDX model were randomized to treatment or control group. The treatment group were gavaged at a volume of 0.1 ml/10g body weight for 4 weeks, while the control group were administered with vehicle at the same dose orally. Tumor volume and body weight were measured every 3 days, and the tumour were removed and weighed after 28 days. The number of mitotic cells and tumor necrosis rate were detected by Hematoxylin-Eosin (HE) staining. Immunohistochemistry (IHC) was used to evaluate the number of apoptotic cells and the expression of VEGFR-2, PDGFR-β, FGFR-1, c-Kit and their phosphorylated proteins, CD 31. Additionally, patients who had progressed during neoadjuvant chemotherapy (NAC) were treated with combination of anlotinib. After four cycles NAC, we performed salvage surgery and maintained with anlotinib. The change of tumor size was evaluated for tumor response. We used IHC and NGS to analyze the expression of drug targets. Results: 21 PDX models were established successfully from 43 samples. Tumor specimens from patients, who had pulmonary metastasis, local recurrence or chemoresistance, were easier to establish PDX models (P < 0.001, P = 0.046, P = 0.013). Six models were selected randomly for anlotinib. After anlotinib administration, the tumor inhibition rates were 18.82%, 45.98%, 85.86%, 83.38%, 84.57% and 86.42%. Anlotinib could not only inhibit the mitosis, induce tumor cell apoptosis and necrosis, but also decrease the expression of drug targets. The expression of VEGFR-2, PDGFR-β and CD31 were positively associated with tumor response. Five patients had received anlotinib during NAC. Four patients had tumor regression (69.4%, 28%, 19%, 8.7%), including two with high expression of VEGFR-2 mRNA or/and PDGFR-β and one with medium expression. Conclusions: Based on the results of PDX models and NGS, we suggested that osteosarcoma with high expression of VEGFR-2 or/and PDGFR-β was sensitive to anlotinib, which was alternative for patients progressed during NAC.
Real-world experience of tyrosine kinase inhibitors in patients (pt) with recurrent bone tumours (BT): A CanSaRCC study.
Authors: Vora Tushar Shailesh , Peretz Soroka Hagit , Noujaim Jonathan Christopher , Marcoux Nicolas , Alcindor Thierry , Karachiwala Hatim , Alvi Saima , Shaikh Furqan , Abdul Razak Albiruni Ryan , Gupta Abha A.
Published: June 2022

11530

Background: Survival after relapse in osteosarcoma (OST), Ewing Sarcoma (ES) and chondrosarcoma (CS) remains dismal. Recent reports suggest a role of tyrosine kinase inhibitors (TKI) including regorafenib (R) and cabozantinib (C). We conducted a retrospective multi-centre pan-Canadian study to assess real-word outcomes with these novel treatments in recurrent BT. Methods: After ethics approval, data from pts treated in 7 different institutions was extracted from the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) Database. Pt characteristics, treatment and outcomes were analyzed. Response was assessed per RECIST 1.1. PFS, OS were estimated using Kaplan-Meier. TTP was defined as time from TKI start to progression. Results: From June 2018-Dec 2021, 44 pts received R or C and best response by histology are listed in Table, with an overall clinical benefit rate of 63.6%. Median time to best response was 2.3 mo (range 1 – 17). 15 pts (34.1%) required dose reduction; most common reasons were hand-foot syndrome (13.6%), mucositis (9.1%) and hypertension (9.1%). At median FU of 6.4 mo (range 1.6 – 29), 25 pts (56.8%) died, 19 (43.2%) were alive with disease (AWD). Median PFS was 4.1 mo (95%CI 2.9 – 5.7), for OST was 5.0 (N = 25, 95%CI 2.6 – 10.6), for ES was 4.1 (N = 10, 95%CI 2-5.9), and for CS 4.0 (N = 9, 1 Progressed). Median OS was 10.5 mo (95%CI 7 – 14). By univariate analysis, age, line of therapy, gender, location of primary, or R vs. C did not correlate with PFS. Conclusions: Consistent with previous published studies, our pan-country real-world analysis shows that TKI have meaningful activity in the setting of recurrent BT with acceptable toxicities. Inclusion in earlier lines of treatment and/or maintenance therapy could be questions for future research. [Table: see text]