bluuebunny/crossref_metadata_2025 huggingface dataset:
Professional development in a Twitter hematology/oncology network for trainees.
Authors: Faisal Muhammad Salman , Anampa-Guzmán Andrea , Desai Aakash , Mohyuddin Ghulam Rehman , Marshall Ariela Lucy
Published: June 2022

11034

Background: While resources exist to address the needs of graduate medical trainees, online resources to assist trainees with specialty-specific professional development have not been fully developed or described in the past. The Hem-Onc Fellows Network (@HemOncFellows) is an online community for hematology-oncology trainees in all stages of training, including medical students, residents, fellows, and doctoral students. The network's goals are to provide professional development in hematology-oncology, create a community and safe space for hematology-oncology trainees, and amplify the voices and needs of trainees. Methods: The @HemOncFellows Twitter account was created in February of 2021. The hashtag #HOFellows was registered and certified with healthcare Symplur. The network hosts Twitter Spaces (TS) with guests every two weeks and distributes a newsletter. Fifteen TS were held between July 2021 and February 2022. For each TS, a specific topic of professional development was discussed. At least one content expert was invited to each TS to provide additional commentary. Demographics of TS participants and newsletter subscribers were gathered and qualitative and quantitative analysis was performed. Results: Since its inception, the Hem-Onc Fellows Network has grown to more than 2200 followers. Symplur has over 500 #HOFellows tweets from November of 2021 to early February of 2022. The network organized 15 TS: 14 in professional development topics and one meet-and-greet for new matched fellows in December. TS had an average of 41 participants per event. Most participants were United States-based but there were participants from 21 countries worldwide. Forty-eight participants attended three or more spaces, including 15 hem-onc fellows and 17 internal medicine residents. The newsletter has 48 subscribers. Conclusions: We demonstrate that implementing a trainee network on Twitter attracted participation and engagement from a diverse pool of trainees worldwide. TS represents a novel educational tool for engaging trainees and facilitating professional development.
Google search engine analytics for cancer immunotherapy: What patients are searching for on the internet and where they find answers.
Authors: Suresh Neeraj , Rajasekaran Karthik
Published: June 2022

11036

Background: Immunotherapy in the treatment of cancer has been on the rise and is on the forefront of current cancer research. As such, patients are increasingly turning to the Internet and online resources to answer their questions. For any given Google search, artificial intelligence and machine learning algorithms generate a “People Also Ask” (PAA) section which returns the most commonly associated questions to the original search query, with corresponding websites to answer those questions. Using a search engine optimization (SEO) tool, we determined the most frequently searched terms and questions regarding cancer immunotherapy online, and the websites used to answer them. Methods: The top Google search queries and PAA questions with associated volume metrics were extracted for the terms “immunotherapy” and “cancer immunotherapy” using an SEO tool. PAA questions and corresponding websites were categorized by specific topic and Rothwell’s classification system. Websites were further quality assessed using the Journal of the American Medical Association (JAMA) benchmark criteria. Results: Global searches for cancer immunotherapy increased significantly each year since 2015. Countries with the most search volume were the U.S. (44%), the U.K. (12%), and India (11%). PAAs (n = 674) and the most frequently searched questions regarding cancer immunotherapy, by average monthly search volume (searches per month), were on: definitions/how it works (n = 6.6K, 21.3%), side effects (n = 4.4K, 14.2%), cost (n = 2.9K, 9.4%), immunotherapy vs. chemotherapy (n = 1.8K, 5.8%), drug options (n = 1.7K, 5.5%), signs immunotherapy is working (n = 1.2K, 3.9%), different types of immunotherapy (n = 1.1K, 3.5%), route of administration (n = 800, 2.6%), efficacy/success rate (n = 800, 2.6%), and effect on life expectancy (n = 300, 1.0%). The top cancers that patients searched immunotherapy treatments for were: lung (n = 1.9K, 23.2%), melanoma (n = 1.5K, 18.3%), pancreatic (n = 700, 8.5%), breast (n = 600, 7.3%), and bladder (n = 500, 6.1%). The most queried immunotherapy drugs were Pembrolizumab/Keytruda (n = 87K), Nivolumab/Opdivo (n = 33K), and Ipilimumab/Yervoy (n = 11.1K). Websites used to answer PAA questions were mostly those of academic institutions (n = 294, 43.6%), commercial organizations (n = 167, 24.8%), and government databases (n = 126, 18.7%). Conclusions: The field of cancer immunotherapy is rapidly evolving and patients often look to the Internet to answer their latest questions. Using our findings, academic institutions, commercial organizations, and physicians involved in multi-disciplinary cancer care can cater their patient communications and websites to more directly align with patients’ most common questions and concerns on immunotherapy.
Generating meaningful peer-to-peer engagement through a mentor-led, small group social learning experience on the evolving standards of care for advanced HER2+ breast cancer.
Authors: Shivakumar Latha , Wongus Rukiya , Haimowitz Steven , Shah Lisa , Ye Amanda , Boehmer Leigh
Published: June 2022

11040

Background: Although the COVID-19 pandemic quickly created a spotlight on distance learning, identifying models that can deliver effective educational programs and best serve the needs of oncology clinicians remains a significant challenge. Methods: We conducted an educational program on the evolving standards of care for advanced HER2+ breast cancer hosted on a novel digital platform that offers a personalized social learning experience which prioritizes engagement, peer-to-peer learning, and mentorship within a small group setting. Results: 87 learners within 10 groups of professionally-connected clinicians participated. Learners progressed through foundational self-study modules, collaborated on asynchronous group challenges, and participated in synchronous live group discussions over six weeks (approximately 4 hours total). Quantitative and qualitative analysis of data extracted from these components highlights the impact of this program (Table). Notably, the learner population was more specialized and engaged than could be expected of a traditional CME program. Feedback suggests strong impact of the live group discussions on learners’ intended practice changes. Additionally, analysis of group challenges and live group discussions revealed several key insights into learner thinking about treatment guidelines, including their differing opinions about the role of surgery/radiation in patient care, uncertainty about the mechanisms of action (MOAs) of discussed therapies, and their apprehension about implementing therapies that may impact the heart and lungs. Conclusions: The outcomes from this analysis highlight the utility of this type of social learning platform to create a safe, supportive learning environment that encourages multiple real-time and asynchronous interactions and shared experiences between clinicians who treat patients with advanced HER2+ breast cancer, as well as offering unique and convenient mentoring opportunities for clinicians interested in leading these digital small groups. Program impact.[Table: see text]
Comparing online engagement and academic impact of lung cancer research: An altmetric attention score and PlumX analysis.
Authors: Muthiah Arun , Muthiah Chandrasekar , Wei Chapman , Khan Hina
Published: June 2022

11044

Background: Social media has proven vital in the rapid dissemination of literature to medical professionals and the public. In recent years, seminal research articles have yielded breakthrough therapies for lung cancer, including targeted drugs and unique immunotherapy-based combinations. New metrics such as the Altmetric Attention score (AAS) and PlumX Impact score capture interactions through social media and other public forums and serve as swifter counterparts to citations, which can take years to accrue. In this study, we characterize and compare AAS, PlumX and traditional bibliometrics (citation count, impact factor [IF]) of the top 100 trending articles on lung cancer. Methods: The 100 articles with the highest AAS featuring the keywords “lung cancer” between 01/2019 and 12/2021 were identified via Altmetric explorer. AAS, open access status, article type, topic, year and continent of publication were collected. PlumX and citation count were identified via Scopus database. Analysis included Spearman correlation coefficients and ANOVA. Results: A majority of the 100 articles were original investigations, of which 40% were RCTs, 22% retrospective cohort, 14% prospective, 9% basic science, 8% cross-sectional and 6% genome-wide association studies. Most articles focused on NSCLC (59%) and were conducted in North America (44%); 13% were in Europe, 36% multi-continental and the remainder < 5% each. PlumX positively correlated with both citation count (p <.001, r =.765) and IF (p <.001, r =.581). AAS did not correlate with citation or IF. Articles on guidelines (p <.001) and screening (p <.001) were associated with higher AAS in comparison to other article types and topics, respectively. Basic science articles were associated with a higher PlumX (p <.001) in comparison to others article topics. Year and continent of publication did not impact PlumX or AAS. Open access status did not correlate with PlumX or AAS. Conclusions: In our study, PlumX scores strongly correlated with citations and IF for recently published articles on lung cancer; this mirrors trends in other specialties. PlumX may be predictive in terms of academic impact, making it valuable to the research community. Though AAS did not correlate with traditional bibliometrics, its association with guidelines and screening articles suggests AAS may reflect interactions amongst a broader community (oncologic and non-oncologic clinicians). With the growing use of social media, the continued exploration of alternative metrics will play a role in understanding readership and fields of interest in lung cancer and in anticipating academic impact.[Table: see text]
The impact of diversity, equity, and inclusion training in an independent community oncology practice.
Authors: Fleming Mark T. , Lewis Tifany , Lyons Kristina , Poole Roshonda , Prillaman Christina
Published: June 2022

11057

Background: Historically, Diversity, Equity, and Inclusion (DEI) efforts have largely been left out of private practice medical facilities – mainly present in large academic hospital centers. Virginia Oncology Associates (VOA), a member of The US Oncology Network, is an independent community oncology and hematology practice specializing in the diagnosis and treatment of cancer and blood disorders. VOA has approximately 600 total employees consisting of physicians and clinical and non-clinical staff. In August of 2020, VOA launched an initiative to foster a culture of inclusion with the creation of its Inclusion Council (IC). Sixteen employees’, both clinical (3 physicians) and non-clinical, were chosen to participate. The council reports to VOA’s joint policy board. Methods: The council partnered with an outside organization, Virginia’s Center for Inclusive Communities, to launch a practice-wide DEI training program focusing on unconscious bias and microaggression. The training was initially planned to be in person, but due to the constraints of the COVID pandemic, the training was performed using a virtual platform. The members of IC attended three two-hour sessions while other staff members and physicians were mandated to participate in at least one training session. After completion of the sessions, a survey was sent to all employees and physicians to measure the impact of DEI training. All employees were also given the opportunity to provide additional, anonymous, written feedback. Results: Table. A total of 169 employees responded. 72% of respondents agreed or strongly agreed that the program increased awareness of unconscious bias and microaggression, 67% felt that the program helps foster a culture of inclusion in the workplace, and 66% of respondents felt that the program met expectations. Conclusions: DEI efforts are vital in all aspects of health care delivery and oncology settings. DEI training met staff expectations and positively fostered a culture of inclusion by bringing attention to unconscious bias and microaggression in a community oncology practice.[Table: see text]
Gemcitabine-docetaxel in patients with relapsed high-grade osteosarcoma after first-line treatment with high-dose ifosfamide: A retrospective multicenter study.
Authors: Pionelli Maria Grazia , Asaftei Sebastian Dorin , Meazza Cristina , Longhi Alessandra , Tamburini Angela , Coccoli Luca , Merlini Alessandra , Cagnazzo Celeste , Tirtei Tirtei , Fagioli Franca
Published: June 2022

11520

Background: Currently, there is no accepted standard chemotherapy regimen for recurrent osteosarcoma. We performed a retrospective study to evaluate the effectiveness, toxicity and clinical benefit of second line therapy with Gemcitabine (G) in combination with Docetaxel (D), in patients with relapsed high-grade osteosarcoma who have been previously treated with High-dose Ifosfamide (HD-IFO) during first-line treatment (ClinicalTrials ID: NCT04651179). Methods: Patients were eligible to the analysis according to the following criteria: episode of first relapse of osteosarcoma, previous first line treatment according to poor responders’ arm of ISG-AIEOP OS 2 Protocol based on methotrexate, cisplatin, doxorubicin and HD-IFO (3gr/m2/day, day 1-5) ± Mifamurtide, presence of measurable disease according to RECIST 1.1, treatment with at least two cycles of Gemcitabine 900 mg/m2/day, days 1 and 8 and Docetaxel 75 mg/m2 day 8 every 21 days. Primary objective: overall survival (OS) at 12 months; secondary objectives: overall response rate (ORR) (complete response + partial response), progression-free survival (PFS) at 6-12 months, toxicity and quality of life. Results: 14 patients were included in the analysis. All patients were previously treated according to poor responders’ arm of ISG-AIEOP OS 2 Protocol, 7/14 (50%) of them received Mifamurtide. Most of patients (12/14, 86%) received 4 GD cycles and the total number of cycles administered was 60. Median OS was 20 months (range 11-69); OS at 12 and 24 months was 84% (95% CI 65-100) and 51% (95% CI 22-79), respectively; ORR were 35,7% after six cycles. Median PFS was 12 months (range 2-69); 6-months and 12-months PFS were 86% (95% CI 67-100) and 56% (30-83) respectively. For 8/14 (57%) patients a surgical approach was feasible after 2 and 6 GD cycles. Previous use of Mifamurtide correlate with a better 6-months PFS rate (100% vs 57%, P = 0.0011). Also, amelioration of ECOG/Lansky score showed a positive correlation with both PFS (P = 0.01) and OS (P = 0.04). No extra-hematological toxicities grade ≥3 was observed according to CTCAE v4.03 criteria. Conclusions: This trial confirms that GD combination has an anti-tumor activity for relapsed high-grade osteosarcoma with a well-tolerated toxicity profile. Furthermore, GD guarantee a surgical tumor remotion for patients with a chemo-resistant disease such as patients previously treated with a poor responders’ arm improving their OS and PFS rate. Promising results for patients previously treated with Mifamurtide need to be confirmed in future trials. Clinical trial information: NCT04651179.
Age as a factor in the molecular landscape and the tumor-microenvironmental signature of osteosarcoma.
Authors: Seeber Andreas , Elliott Andrew , Modiano Jaime , Untergasser Gerold , von Mehren Margaret , Rosenberg Andrew , Khushman Moh'd , Dizon Don S. , Riedel Richard F. , Trent Jonathan C. , Zimmer Kai , Lagos Galina , DeNardo Bradley , Sarver Aaron , Puccini Alberto , Walker Phillip , Oberley Matthew James , Korn Wolfgang Michael , Wolf Domink , Kocher Florian
Published: June 2022

11525

Background: Osteosarcoma (OS) incidence is characterized by a bimodal age distribution, with peaks in early adolescence and in adults > 65 years of age. In contrast to adolescents, OS in adults is frequently considered as a secondary neoplasm (i.e., transformation of Paget´s disease of the bone, radiation induced). Yet, the literature is scarce regarding the impact of age on the molecular landscape of OS. Herein, we sought to explore the association between age and the genomic profile as well as the tumor immune microenvironment (TME) in a large cohort of OS patients. Methods: 208 specimens were centrally analysed at the Caris Life Sciences laboratory with DNA seq (NextSeq, 592 gene panel or NovaSeq, whole-exome sequencing), RNA seq (Archer fusion panel or whole-transcriptome sequencing) and immunohistochemistry (IHC). RNA deconvolution and differential expression analyses were performed using the Microenvironment Cell Populations counter method for quantification of immune cell populations and gene expression profiling. The cohort was stratified into three distinct age groups (< 25 years [n = 83], 25-45 years [n = 58], > 45 years [67]). Results: Overall, the most frequently detected mutations were in TP53 (37%), RB1 (13%), ATRX (9%), TERT (6%), PTEN (5%), PIK3CA (4%) and KMT2D (3%). Copy number alterations were most frequently detected in CDK4 (12%), LRIG3 (11%), FLCN (11%), MDM2 (9%), CCND3 (9%), VEGFA (8%), TFEB (8%). Interestingly, age-based stratification revealed an increased frequency of FLCN (19.7 vs 4.7%, p < 0.01), CCND3 (13.9 vs 3.1%, p < 0.05), and HSP90AB1 (11.3 vs 0.0%, p < 0.01), alterations in patients < 25 years compared to > 45 years. TME analysis revealed that patients > 45 years have decreased B-cell abundance compared to patients < 25 years (2.9-fold decrease, p < 0.05) and 25-45 years (4.8-fold decrease, p < 0.05). Although not statistically significant, median transcriptional expression of PD-L1 was numerically increased in patients > 45 years (1.8-fold compared to 25-45 years, p = 0.17; 2.0-fold compared to < 25 years, p = 0.27), which was consistent with increasing rates of IHC PD-L1 expression with age (5.3%, 9.4%, and 17.5%, respectively, p = 0.06). Conclusions: To the best of our knowledge, this study represents the largest cohort of molecularly characterized OS. Age-associated differences in the genetic landscape and TME composition, including increased gene amplifications observed in younger patients and decreased B-cell abundance in older patients, might suggest fundamental underlying molecular and biological differences.
A phase 2 study of anti-PD-L1 antibody (atezolizumab) in grade 2 and 3 chondrosarcoma.
Authors: Salkeni Mohamad Adham , Conley Anthony Paul , Chen James Lin , Davis Elizabeth J. , Burgess Melissa Amber , Abdul Razak Albiruni Ryan , Moore Nancy , Ferry-Galow Katherine V. , Fino Kristin K. , Fung King Leung , Parchment Ralph E. , Foster Jared C. , Rosenberger Christina , O'Sullivan Coyne Geraldine Helen , Takebe Naoko , Sharon Elad , Doroshow James H. , Chen Alice P.
Published: June 2022

11528

Background: Chondrosarcoma is one of the most common bone malignancies in adults, and the third most common in pediatric patients (pts). The most prevalent subtype, conventional chondrosarcoma, is a slow growing tumor that is historically known to be refractory to chemotherapy. Anecdotal reports indicated a role for anti-PD-(L)1 in the treatment of this disease. This is the first prospective report on the efficacy of the PD-L1-targeting agent, atezolizumab, in this rare disease. Methods: Patients (pts) ages 2 and older with unresectable grade 2 or 3 conventional chondrosarcoma were eligible. No prior anti-PD-(L)1 treatment was allowed, otherwise pts were eligible irrespective of prior therapies as long as protocol-specified washout period requirements were met. Pts received atezolizumab 1200 mg (15 mg/kg with 1200 mg cap in pediatric pts) once every 21 days. Imaging was carried out at end of cycle 3, and then every two cycles. Research biopsies were collected from adult pts prior to C1D1, prior to C3D1, and at progression. Immuno-pharmacodynamic (IO-PD) studies were performed on paired tumor samples and circulating immune cells to help elucidate signaling pathways mediating the immune response, with focus on subsets of effector cells in the tumor microenvironment. Results: A total of 9 pts (7 males, 2 females) were enrolled in 6 centers across the US and Canada. Six pts were Caucasian/White, 1 Asian, 1 Hispanic, and 1 unknown. Median age was 49 years (42-72). No objective responses were seen. Three pts (33%) experienced disease stability (SD) per RECIST 1.1, for a median duration of 21 weeks as of data cutoff (January 2022). A patient with SD remains on active treatment (tx) for 35 weeks. Three patients had no tx-related adverse events (AEs). Six pts (67%) experienced at least one tx-related AE. Two patients experienced > G2 AEs, but only one was considered tx-related (lymphopenia). Immune-related AEs were all G1/2 and included hepatitis (2), hypothyroidism (1), hyperthyroidism (1), and maculopapular rash (1). IO-PD studies are ongoing and will be reported at the conference if available. Conclusions: Atezolizumab was well-tolerated but demonstrated limited activity in this cohort of pts with few treatment options. Ongoing IO-PD studies will provide insight into atezolizumab’s effect upon immune cell content and activation in the tumor microenvironment that will help design future immunotherapy trials in this disease and other sarcoma types. The study was funded by NCI Contract HHSN261201500003I. Clinical trial information: NCT04458922.
Checkpoint inhibitor and multireceptor tyrosine kinase inhibitor combination in relapsed refractory sarcomas: A single institution series.
Authors: Mittal Nupur , Seyboth Brian , Kent Paul
Published: June 2022

11529

Background: Adolescent and young adults (AYA) with primary metastatic and relapsed bone and soft tissue sarcomas (BST) have poor prognosis with progression free survival (PFS) rates < 15% and overall survival (OS) < 20%. These outcomes have not improved in the past three decades, highlighting the need for new treatment paradigms. Immunotherapy is effective for multiple malignancies via blockade of CTLA4 or PD-L1 by immune checkpoint inhibitors (CPI), like nivolumab (NIVO). Sarcomas often express PD-L1 as part of their complex pathogenic pathway. Additionally, combination with oral targeted therapies is an emerging strategy for adult malignancies. Encouraging early phase results with multi-tyrosine kinase inhibitors (TKI) of several pathogenic sarcoma pathways – including lenvatinib (LEN), cabozantinib (CABO), and pazopanib – have prompted our team to offer CPI in combination with a TKI for BST patients without chemotherapy options. Methods: Retrospectively identified AYA patients with relapsed heavily pre-treated BST who received CPI/TKI combination at our institution between January 2018 to date. Results: This is the first reported series of prolonged survival in metastatic and multiply relapsed BST with CPI and TKI therapy. Table summarizes the demographics, disease features, and survival for all patients. The regimen was well tolerated in all patients, except for a rash (n = 1) that resolved by reducing the CABO dose by 25%. All patients had previously been offered palliative care before this regimen. Conclusions: Our preliminary experience with CPI/TKI combination in multiply relapsed BST shows a PFS exceeding prior PFS periods with other therapies for all patients. The overall survival is more than historical controls for initial metastatic ASPS, initial metastatic EWS, and recurrent metastatic OST. Our report will inform colleagues about the potential of CPI/TKI combination for these patients with few options. [Table: see text]
Subclonal somatic copy number alterations emerge and dominate in recurrent osteosarcoma.
Authors: Kinnaman Michael David , Zaccaria Simone , Makohon-Moore Alvin , Gundem Gunes , Arango Ossa Juan E. , Bouvier Nancy , Dela Cruz Filemon S. , Hameed Meera , Glade Bender Julia Lynne , Tap William D. , Meyers Paul A. , Papaemmanuil Elli , Kung Andrew , Iacobuzio-Donahue Christine A
Published: June 2022

11533

Background: Multiple large-scale tumor genomic profiling efforts have been undertaken in osteosarcoma, however little is known about the spatial and temporal intratumor heterogeneity and how it may drive treatment resistance. Methods: We performed 30-80x whole genome sequencing (WGS) of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. A set of high confidence single nucleotide variants (SNV), copy number alterations (CNA), structural variations (SV) were called for each sample using our pediatric expanded genomics pipeline and an evolutionary analysis was performed using a custom pipeline of computational tools. Results: Of the 8 patients in our cohort, 4 had localized disease at diagnosis (OSCE4, OSCE5, OSCE6, OSCE9) and 4 had metastatic disease at diagnosis (OSCE1, OSCE2, OSCE3, OSCE10). There were 17 samples from primary sites, 7 were pretreatment biopsies, 10 from on therapy primary resections. 20 samples came from metastatic sites, 15 of which were from lung metastases. Driver gene SNV’s were identified in 5 of 8 patients, including TP53 (OSCE1), ATRX (OSCE3, OSCE10), RB1 (OSCE4), and CDKN2A (OSCE9). No new driver SNV’s emerged post-therapy in any patient. HATCHet, an algorithm which infers clone specific copy number alterations, identified subclonal CNAs in all but one patient (OSCE2). In the 7 patients with subclonal CNAs, 6 had two copy number clones identified, and 1 patient (OSCE10) had three copy number clones identified. In 5 patients (OSCE1, OSCE4, OSCE5, OSCE6, OSCE10) there is a copy number clone that is subclonal in the primary tumor which emerges and dominates at subsequent relapses. The resistant clone in each of these cases had either MYC gain/amplification. Amplifications in CCNE1 (OSCE1), RAD21 (OSCE4, OSCE5, OSCE10), VEGFA (OSCE1, OSCE9), IGF1R (OSCE6) were also identified as potential drivers in the resistant copy number clones. In two of these patients (OSCE1, OSCE6), the treatment resistant subclone becomes the dominant copy number clone by the time of primary resection. SNV based phylogenies revealed monoclonal and polyclonal seeding of metastases and monophyletic and polyphyletic modes of dissemination. Over half the new mutations acquired in recurrent disease were attributed to HRD or cisplatin mutational signatures. Conclusions: Subclonal copy number clones emerge and dominate in relapsed osteosarcoma, with MYC gain/amplification a defining characteristic in our cohort. Selective pressure from neoadjuvant chemotherapy reveals this clone at the time of primary resection, implying genomic profiling at this timepoint may be more reflective of its metastatic potential. [Table: see text]
A randomized phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumors.
Authors: Kim Hyung-Don , Yoo Changhoon , Ryu Min-Hee , Kang Yoon-Koo
Published: June 2022

11538

Background: Resumption of imatinib is one of the available therapeutic options for patients with gastrointestinal stromal tumors (GIST) refractory to tyrosine kinase inhibitors (TKIs). Intermittent dosing of imatinib was suggested to delay outgrow of the imatinib-resistant clones in a preclinical study. Methods: A randomized phase 2 study was performed to evaluate the efficacy and safety of continuous or intermittent schedule of imatinib in GIST patients whose disease had progressed to at least imatinib and sunitinib. Patients were randomly assigned (1:1) to the intermittent dosing group that received 400mg daily imatinib based on a 1 week-on and 1 week-off schedule or the continuous dosing group that received imatinib 400mg daily without drug holiday. Disease control rate (DCR) rate at 12 weeks was the primary endpoint. Plasma samples were collected for circulating tumor DNA analysis at baseline, at 3 months of continuous or intermittent imatinib treatment and at the time of progressive disease. Results: Fifty patients received at least one dose of imatinib and were included in the full analysis set. Most patients (n = 46) had received prior regorafenib. DCR rate at 12 weeks was 34.8% and 43.5% in the continuous and intermittent groups, respectively. Median progression-free survival was 1.68 months and 1.57 months in the continuous and intermittent groups, respectively. The frequency of any grade anorexia, dysphagia, diarrhea, decreased neutrophil was lower in the intermittent group, whereas that of abdominal pain was higher in the intermittent group. Two patients in the continuous imatinib group underwent dose modification, and there was no patient who discontinued the study treatment because of adverse events related to study treatment. Conclusions: We confirmed that imatinib re-challenge was effective in TKI-refractory GIST patients. Intermittent dosing schedule may also be a clinically feasible treatment option for imatinib resumption in TKI-refractory GIST patients. Clinical trial information: NCT02712112.
Clinical utility of circulating tumor DNA sequencing with a large panel in patients with advanced soft-tissue sarcomas.
Authors: Blanchi Julie , Taleb Sofiane , Bayle Arnaud , Verret Benjamin , Toulmonde Maud , Spalato Mariella , Alame Melissa , Khalifa Emmanuel , Italiano Antoine
Published: June 2022

11550

Background: Preliminary studies have suggested that the detection, quantification, and profiling of ctDNA in patients with sarcoma is feasible and may improve prognostication, measure treatment response, and detect relapse. However, data related to impact of ctDNA profiling to tailor therapy in patients with advanced disease are lacking. Methods: Patients with advanced soft-tissue sarcomas (STS) have been included in two ongoing institutional molecular profiling studies (BIP: NCT02534649, STING: NCT04932525). Genomic analysis (ctDNA in all cases and tissue when available) was performed by using the Foundation One Liquid CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability status). Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumour board dedicated to precision medicine, attended by experts in clinical oncology, molecular biology, and clinical genetics. Actionable targets were defined by the MTB according to the existing level of evidence (ESCAT), and molecular-based treatment suggestions were proposed where possible. Results: Between December 2020 and August 2021, 98 patients with metastatic STS underwent ctDNA profiling. Median time to assay results was 12 days. Results were contributive for 86 patients (88%). At least one actionable target (range 1-4) was detected in 35 patients (36%) including high tumor mutational burden (> 16 mutations/Mb) for 1 patient (1%) and alteration of the DNA repair response pathway for 12 patients (12%). Overall, the MTB recommended a matched therapy for 27 patients (28%). 40 patients underwent also NGS of tissue besides ctDNA profiling. The number of actionable alterations was similar in 26 (65%), whereas it was higher in tissue for 10 (25%) and in liquid for 4 (10%) patients. Conclusions: This large-scale study demonstrates that liquid biopsy with a large NGS ctDNA panel is an efficient approach to match patients to genomically directed clinical trials/targeted therapies in patients with advanced STS. Outcomes of patients treated with matched therapy will be presented at the meeting.
Accounting for the high enrollment of African Americans in Winship Cancer Institute’s myeloma clinical trials.
Authors: McClary Tekiah , Blee Shannon M. , Avinger Anna , Switchenko Jeffrey M. , Dixon Margie D. , Pentz Rebecca D.
Published: June 2022

12016

Background: Multiple myeloma (MM) is twice as common in African Americans (AA) as in Whites, yet AA make up only 5% of multiple myeloma (MM) clinical trial participants nationwide. Multiple studies have attempted to identify the reasons why AA are underrepresented in clinical trials and have discovered that sociodemographic factors, a lack of understanding, mistrust of sponsors, and a variety of opportunity barriers all contribute to AA underrepresentation in clinical trials. At one cancer center, African Americans make up 33% of those enrolled in MM clinical trials. To begin to account for this success in enrolling AA in myeloma clinical trials, a survey was designed to determine whether the major barriers to AA clinical trial participation existed at this cancer center. Methods: The survey was open to any AA patient who had consented to a clinical trial. The Trust in Medical Research scale (TMR) developed by Hall et al., the Human Connection (THC) scale developed by Mack et al., and the Duke Intrinsic Religiosity Scale (DUREL) were the three main scales used in the survey. Adapted assessment questions from Advani et al were used to assess the importance of side effects in deciding to participate in clinical trials. Results: We offered the study to 76 patients and 80% (61/76) participated. The mean TMR score was 15.0 which is significantly greater than the 11.6 score observed for AAs at other institutions (p < 0.001). The mean human connection score was 57.7 which is significantly greater than the 54.6 observed in the population of the Mack study, which accrued mostly white participants (p < 0.001). The Pearson correlation coefficient between the TMR score and the human connection score is 0.37, indicating a significant positive correlation between human connection scores and trust scores (p-value = 0.002). The average score for the intrinsic religiosity section of the DUREL scale was 13 (score of 15 indicates high religiosity). The average score of importance of side effects was 8.574, significantly higher than the Advani AA response of 6.7 (p-value < 0.001). Conclusions: African Americans enrolled in clinical trials at the high enrolling cancer center had higher THC and TMR scale scores than reported nationally, both helping to facilitate trial enrollment. The high intrinsic religiosity score observed suggests that high religiosity had no impact on clinical trial participation, nor did concern about side effects. Furthermore, a high THC score was associated with a high trust score. Since this THC scale assesses whether participants believe their doctors listen carefully, care about them, offer hope, provide clear explanations, and so on, establishing a human connection may be one way to increase AA trust in providers, increase AA clinical trial enrollment and overcome other barriers.
Medical assistance in dying (MAiD) in patients with cancer.
Authors: Moore Sara , Thabet Chloe , Wheatley-Price Paul
Published: June 2022

12028

Background: Medical assistance in dying (MAiD) was legalized in Canada in 2016. Cancer accounts for 60-70% of MAiD cases, though little is known about the demographic profile, cancer diagnoses, and treatments received in patients with cancer who pursue MAiD. We reviewed all patients with cancer who underwent MAiD through a large regional MAiD program, in order to better understand this population and identify gaps in the current system of care delivery. Methods: All patients with cancer who received MAiD through the Champlain Regional MAiD Network (CRMN) from June 1 2016 – November 30 2020 were reviewed. The CRMN provides the majority of MAiD services covering a population of 1.3 million in Eastern Ontario. Baseline demographic factors, diagnostic information, and treatment details were collected by retrospective review. The primary endpoint was the proportion of patients with an oncology consultation prior to MAiD. Results: During the study period, 255 patients with cancer underwent MAiD. Baseline characteristics included: median age at death 71 (range 31-100), 51% male, 56% married/common-law. The most prevalent solid tumors were gastrointestinal [GI] (n = 77, 30%), lung (n = 47, 18%), and genitourinary [GU] (n = 35, 14%). Most patients (n = 201, 79%) had metastatic disease at the time of MAiD. Of those without metastatic disease at time of death, common tumor sites included central nervous system (42%) and head and neck (23%). The majority of patients (n = 229, 89%) had seen an oncology specialist prior to MAiD; 226 (88%) had seen a systemic oncologist (medical, hematologic, or gynecologic oncologist), and 189 (69%) a radiation oncologist. Seventy-three percent of patients were followed by a systemic oncologist within 90 days of MAiD, and 44% within 30 days of MAiD. At least one line of systemic therapy was received by 159 (62%) patients, 138 (54%) received radiotherapy, and 61 (24%) best supportive care alone. Median time from last systemic therapy to MAiD was 85 days, and from last radiation therapy to MAiD was 137 days. Palliative care assessed at least 213 patients (84% [8% unknown]). Common reasons for pursuing MAiD included disease-related symptoms (33%), fear of future suffering or disability (19%), and ability to control the time and manner of death (17%). Among 26 patients who had not seen an oncologist, median age was 84 (range 61-100), 77% male, 42% GI primary / 19% GU / 15% lung. Most had seen a palliative care specialist (n = 23, 88%), and in the remaining 3 patients palliative care involvement was unknown. Conclusions: MAiD is a relatively new option for patients with cancer in Canada. The vast majority of patients with cancer who pursue MAiD are diagnosed with advanced/incurable disease, and most have met with an oncology specialist. As cancer treatments become more effective and more tolerable, collaboration between oncologists and MAiD providers is required to ensure patients are well informed of treatment options prior to MAiD.
Geographic disparities in breast cancer mortality and place of death in the United States from 2003 to 2019.
Authors: Clemons Kelli , Blackford Amanda L. , Gupta Arjun , Agarwal Parul , Donehower Ross C. , Marrone Kristen , Hussaini Syed
Published: June 2022

12034

Background: Breast cancer is the 2nd leading cause of cancer-related death in women with existing barriers in preventive services, access to treatment, and end-of-life care. There are unique sociopolitical challenges to rural healthcare with gaps in national health funding and hospice infrastructure. We investigated rural-urban disparities in age-adjusted mortality rates (AAMRs) and place of death in individuals dying from breast cancer. Methods: CDC WONDER database was utilized to analyze deaths from breast cancer from 2003 to 2019 using population classification per 2013 US Census: large metropolitan (≥1 million), small- or medium-sized metropolitan (50,000-999,999), and rural areas (< 50,000). We extracted AAMRs by geographic area, age, and race/ethnicity. We estimated annual percentage changes (APC) in AAMR using robust linear regression models of the log-scale AAMR, including population size as weights, and assessed differential changes over time by geographic area with interaction tests. We estimated the percent of all deaths occurring in medical, hospice, and nursing facilities, and home. Odds ratios (OR) for the association between each place of death and individual-level characteristics were calculated using logistic regression, adjusting for year of death. Differential changes in place of death over time by geographic region were assessed with interaction tests. Results: From 2003 to 2019, there were 676,532 breast cancer-related deaths (52.9% large metro, medium/small metro 30.3%, rural 16.8%). Total AAMR declined from 39.8 to 30.9 during this period with rural areas noting least improvement (APC -1.24, 95% CI [-1.39, -1.09], p < 0.001 for time trend) compared to large metropolitan (APC -1.74, 95% CI [-1.63, -1.46]). Non-Hispanic Black women had higher AAMRs among all racial/ethnic groups. Across all years, women in large metropolitan (OR 2.02, 95% CI [1.96, 2.07]) and medium/small metropolitan (OR 2.19, 95% CI [2.12, 2.25]) had higher odds of dying in a hospice facility compared to rural areas. Rural women died least often in a hospice facility (9.7% vs 14.5% large metropolitan vs 16.9% medium/small metropolitan in 2019), more often in a nursing facility (19.2% vs 12% large metropolitan vs 13.9% medium/small metropolitan) and slightly more often at home (44.6% vs 41.7% large metropolitan vs 43.4% medium/small metropolitan). Women in large metropolitan areas were most likely to die in a medical facility. Conclusions: Rural women with breast cancer experienced greater mortality and least annual improvement, with notable disparities in place of death. Our findings support interventions to improve access across cancer care continuum and congressional policy to urgently re-invest in cancer care access in rural areas.
Modified CARG score using data from the electronic health record to predict chemotherapy toxicity in older adults.
Authors: Martin Jasmine L , Wu Kathie , Gupta Mudit , Johns Alicia M , Adonizio Christian S.
Published: June 2022

12038

Background: Older adults starting chemotherapy are at greater risk of toxicity compared with younger patients. Additional tools are needed to aid in management decisions for this population. The Cancer and Aging Research Group (CARG) chemotherapy toxicity calculator is one such tool, which stratifies older adults into high, intermediate, or low risk for chemotherapy toxicity (Hurria, A., Mohile, S., Tew, W. P., & et al. (2016). Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. Journal of Clinical Oncology, 34(20), 2366–2371. https://doi.org/10.1200/jco.2015.65.4327). This tool relies on a face-to-face encounter to ask questions, e.g. “How is your hearing?” or “Can you take your own medicines?” in addition to lab values such as hemoglobin and creatinine clearance. We modified the CARG chemo toxicity calculator to include data points which could be pulled from the electronic health record (EHR) without the need for a face-to-face encounter to assess for an association with emergency department (ED) visits and hospital admissions. Methods: Retrospective data analysis was conducted using the EHR of patients over age 65 diagnosed with a solid tumor from 1/1/2019 to 12/31/2020 who started chemotherapy. A modified CARG score was calculated using age, cancer type, number of drugs, hemoglobin, creatinine clearance, and falls within the past 6 months. The remaining items needed to calculate the complete CARG score were excluded since they were not accessible in the EHR. We assessed ED visits leading to admission, ED visits leading to discharge, direct admissions, and the total of all 3 visit types for all patients. Results: A modified CARG score was calculated for 763 patients. Multiple models were evaluated and negative binomial distribution was found to be the best fitted for our data. For every one unit increase in our calculated score the number of ED visits which lead to hospital admission increased by 6% (p-value = 0.0156). Additionally, there was a 5% increase in combined ED visits, ED visits leading to admission, and direct admissions for every one unit increase in risk score (p-value = 0.0063). ED visits that did not lead to admission were found not to have an association with the risk score (p-value= 0.1263). (Table) Conclusions: A modified CARG score using data obtained from patients’ EHR had a statistically significant association with increased ER visits that resulted in hospital admission and with the total of ED visits leading to admission, ED visits leading to discharge, direct admissions. Using these outcomes as a surrogate for toxicity, we deduce that a simple tool could be used to predict chemotherapy toxicity in older adults. [Table: see text]
Deficit Accumulation Frailty Index (DAFI) scores and acute myeloid leukemia outcomes.
Authors: Lai Catherine , Conway Olivia , Lee Minji , Le-Rademacher Jennifer , Mandelblatt Jeanne S. , Klepin Heidi D.
Published: June 2022

12040

Background: Novel strategies are needed to assess frailty in the context of therapy decisions for older adults with acute myeloid leukemia (AML). Our objectives were to describe pre-treatment DAFI scores for older AML patients treated on clinical trials and explore their relationship with treatment outcomes. Methods: We conducted a exploratory analysis utilizing data from two clinical trials of adults aged ≥60 years with newly diagnosed AML (Alliance/CALGB 11001 [intensive therapy] and Alliance/CALGB 11002 [non-intensive therapy]). We included the subset of patients in each trial enrolled on geriatric assessment companion studies (Alliance/CALGB 361006, 361101). A DAFI score was calculated for each patient using 51 variables including demographic, geriatric assessment, and laboratory data derived from the geriatric assessment. Individuals with ≥90% items were included (consistent with other studies); DAFI scores ranged from 0 to 1 and were evaluated using established categories (0- <.2 [robust]; 0.2-<.35 [pre-frail]; 0.35+ [frail]) and as a continuous score. Associations between DAFI scores and toxicity and overall survival (OS) were evaluated with Fisher’s exact-testing and Kaplan Meier/cox proportional hazards, respectively. Results: The median age was 68 years (range 61, 82) and 72 years (range 61, 92) for those getting intensive (N=31) and less intensive therapy (N= 75), respectively. Individuals in the intensive study had a median pre-treatment DAFI score of 0.15 (range 0.05, 0.31) and were all categorized as robust (75%) or pre-frail (25%). There was no significant difference in median OS (14.6 vs. 14.7 months) or non-hematological grade 3+ adverse events (AEs; 85% vs. 89%) between robust vs. pre-frail individuals in this trial, respectively. However, pre-frail adults experienced a trend towards greater grade 4 non-hematological toxicity than robust individuals (67% vs 26%, p=0.05). In the non-intensive trial, the median DAFI score was 0.24 (range 0.04, 0.48) and most individuals were pre-frail (49.3%) or frail (17.3%). Non-hematologic grade 3+ AEs did not vary by DAFI group, 88% robust, 95% pre-frail, and 77% frail (p=0.15). Median OS was 7.4, 10.8, and 6.3 months for robust, pre-frail, and frail respectively (p=0.17). Adjusting for age, each 0.1 increase in DAFI score was associated with increased mortality hazard (HR 1.8, 95% CI 1.0-3.2). Conclusions: DAFI score calculation provides a potential novel strategy for categorization of frailty in AML. In our assessment, higher DAFI scores were associated with toxicity during intensive induction and mortality in the less intensive setting. This method should be studied in larger samples randomized by treatment intensity. Support: UG1CA189823; Bayer Healthcare/Berlex (CALGB 11001); NCT01253070 (CALGB 11001). Clinical trial information: NCT01253070, NCT01420926.