bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.