bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the educational needs for a community-based hematology/oncology career: A national needs assessment.
Authors: Agrawal Shubham , Patell Rushad , Dodge Laura E. , Pegher Jennifer W , Coleman Robert L. , Waterhouse David Michael , Roberts Daniel Aaron , Rangachari Deepa 
Published: June 2023

11011 Background: Fellowship training is largely rooted in academic medical centers, though many graduates will ultimately pursue careers in community-based settings. We initiated a national survey of hematologists/oncologists practicing in community or academic-community hybrid settings to understand providers’ educational needs. We hypothesized that the current model of fellowship training is not optimized for those pursuing community-based hematology/oncology careers. Methods: An electronic questionnaire was developed surveying current attitudes and practices of community-based hematologists/oncologists. Survey participants from across the United States were contacted via professional organizations. We primarily assessed whether survey participants received any specific training during fellowship for community-based practice. Participants were also surveyed regarding whether such training may have affected their preparation. Relative risk (RR) and 95% confidence intervals (CI) were calculated using modified Poisson regression with robust error variance adjusted for: time in clinical practice ( < 10 years), size of graduating fellowship training program ( > 5), board certification (hematology and oncology vs. either), and training program geographic location (by region) to identify factors associated with receiving community oncology-specific training. Results: Of the preliminary cohort of 120 participants from across 25 states, 66% were male, 69% identified as White, and 69% had been in practice for > 10 years. Less than half (43.2%, binomial 95% CI 34.6%-52.2%) received any training for a career in a community-based setting. Participants identified rotations in community settings (48%), direct mentorship from community-based physicians (41%), and longitudinal clinic in a community setting (39%) as experiences that would have been valuable. Specific curricula of interest included: medical operations and administration (67%), health policy (38%), and quality improvement (30%). Respondents in clinical practice for < 10 years were more likely to have received any community oncology-specific training (RR 2.02, 95% CI 1.10–3.72); other factors were not significantly associated with the primary outcome (P > 0.05). Conclusions: National trends indicate a growing need for hematology/oncology graduates in community-based settings. Our study demonstrates substantial unmet needs as they relate to training fellows destined for careers in community-based practice. Prospective design of clinical training and curricula emphasizing longitudinal exposures to and key aspects of health care delivery in the community setting are paramount to achieving optimal, goal-concordant hematology and oncology training.
Early introduction to clinical radiation oncology through a self-directed competency-based medical student curriculum.
Authors: Claunch Cheryl , Dalwadi Shraddha , Wang Jarey , Ludwig Michelle Suzanne 
Published: June 2023

11038 Background: Specialty training is not traditionally incorporated into standard medical education and there is a deficiency in exposure to Radiation Oncology for “last minute” interested candidates, particularly from underrepresented backgrounds. Therefore, we implemented MERAO-200, an introductory 2-week in-person and virtual medical education curriculum without clinical prerequisites to facilitate early introduction to the field of Radiation Oncology and report its effect on student comfort and familiarity with radiation planning and contouring. Methods: Clinical students were enrolled in a 2-week elective without clinical prerequisites that integrated both clinical activities and self-directed learning through virtual contouring modules. The virtual curriculum was designed around three modules available on EduCase. A survey was conducted after completion of the modules that solicited self-identifying information and to assess their efficacy in increasing understanding of basic contouring skills. Paired t-tests were used to compare pre- and post-elective assessment results. Results: Twenty-three total students have completed MERAO-200 from Fall 2020 to Spring 2023. Of those, 15 submitted the survey. Eight (53%) students did not answer self-identifying information such as gender, race, ethnicity, or country of origin. Four (27%) students identified as Asian and 3 (20%) as white. No students identified as Hispanic, Latino or Spanish origin. Seven (46%) students identified as having USA as country of origin. Seven (47%) students reported interest in radiation oncology, medical oncology or surgical oncology. Three (20%) students were MS2, 7 (47%) were MS3, and 5 (33%) were MS4. Overall, there was a significant increase in comfort level using radiation planning software (p = 1.1e-4) as well as ability to find relevant contouring references (p = 4.2e-5). Knowledge of the anatomy and contouring principles also improved for the three modules: eye and brain (p = 2.8e-7), high grade glioma (3.2e-6), and head and neck nodal stations (4.5e-6). CNS module difficulty on a scale of 1-10 had a median difficulty score of 7 (range 3-8) and head and neck module difficulty was a median of 7 (range 3-10). Conclusions: Implementation of MERAO-200 improved medical student exposure to the field of Radiation Oncology and improved medical student comfort and familiarity with radiation planning and across all disease sites covered. More outreach work needs to be done to facilitate inclusion of minority student populations and students from underrepresented backgrounds. Early introduction at the medical student level could be a pathway to improve disparity in the field of Radiation Oncology.
Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc).
Authors: Reichardt Peter , Andreou Dimosthenis , Flörcken Anne , Groß Thorben , Richter Stephan , Kessler Torsten , Kortüm Martin , Schmidt Christian Andreas , Kasper Bernd , Wardelmann Eva , Benedict Atzler , Sookthai Disorn , Mueller Daniel Wilhelm , Pink Daniel 
Published: June 2023

11500 Background: Programmed death-1 (PD-1) inhibitors alone have modest activity in the treatment of most STS. A possible synergistic effect of combined trabectedin with PD-1 inhibitor nivolumab has been previously reported. Herein we evaluated the efficacy and safety of trabectedin plus nivolumab as a second-line treatment of patients with anthracycline-pretreated metastatic or inoperable STS. Methods: The prospective, explorative, two-group, non-randomized phase II NiTraSarc trial enrolled patients with advanced lipo- or leiomyosarcomas (Group A; GA) or with non-L-sarcomas (Group B; GB). Patients were initially treated with 3 cycles of trabectedin 1.5 mg/m2, followed by the combination of trabectedin 1.5 mg/m2 plus nivolumab 240 mg in a so-called “late combination cohort” (LCC) for up to 16 cycles. After positive results of a preplanned interim analysis, patients received the combination therapy already starting from Cycle 2 in an “early combination cohort” (ECC). Primary efficacy endpoint was progression-free survival rate after 6 months (PFSR6) according to RECIST v.1.1. A central pathological assessment (CPA) was done from tumor specimen from all patients. Updated results according to cpa are presented. Results: A total of 92 patients were recruited in the trial: 43 patients in GA and 49 in GB. In GA, 28 patients (63%) had leiomyosarcoma and 15 (37%) had liposarcoma. Most common sarcoma types in GB were pleomorphic (n = 12), spindle cell (n = 11), fibromyxoid (n = 6), synovial (n = 5) and epithelial (n = 4) sarcoma. After median follow up of 16.6 months, overall PFSR6 as per CPA in GA was 47.6% (60% in LCC vs 36.4% in ECC) and 14.6% in GB. Median PFS was numerically higher in GA compared to GB (5.5 vs 2.3 months) and even longer in LCC vs ECC (9.8 vs 4.4 months). Median overall survival was more than three times longer in GA vs GB (18.7 vs 5.6 months) and, again, longer in LCC vs ECC (24.6 vs 13.9 months). Safety trabectedin and nivolumab was consistent with the safety profiles of each drug alone with no relevant new findings for the combination or between LCC and ECC. Conclusions: Our study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas. There is a significant difference between ECC and LCC in terms of PFSR6, PFS and OS. The results in patients with non-L-sarcomas do not justify further investigation of this combination. Clinical trial information: NCT03590210 .
The clinical value of tumor-informed minimal residual disease detection in sarcoma.
Authors: Fu Yiwei , Shen Jingnan , Huang Gang , Zou Changye , Xie Xianbiao , Shi Xiaoliang , Jian Qijie , Huang Jintao , Pang Fei , Yin Junqiang 
Published: June 2023

11510 Background: The high recurrence and metastasis rates lead to poor survival of patients with sarcoma. At present, circulating tumor DNA-based minimal residual disease (MRD) has been studied in varies solid tumors and proved to be valuable in guiding treatment and predicting recurrence, but its application in sarcomas is rarely reported. Methods: Tumor tissue samples were used for whole exome sequencing (WES) and clonal mutations were selected for the customized MRD panel. Blood samples were collected for MRD detection. Experiments were conducted at OrigiMed, a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Results: A total of 84 sarcoma patients including 47 bone tumor (BT), 32 soft-tissue sarcoma (STS), and 5 undifferentiated small round cell sarcoma (USRCS) patients were enrolled. Patients consisted of 49 (58.3%) males and 35 (41.7%) females, with a median age of 23 years old (1-85 years old). Based on WES, we found that 64% (4936/7715) of the mutated genes were unique to each patient, and 70.4% (859/1220) of selected tumor-informed single nucleotide variants (SNV) were variants with unknown significance, suggesting that tumor-informed MRD is superior to panel-based MRD in sarcomas. In this cohort, 78.6% (66/84) of patients successfully constructed MRD panels, including 85.1% (40/47) of BT patients, 75% (24/32) of STS patients, and 40% (2/5) of USRCS patients. The main reason for failure was the scarcity of SNVs detected. Preoperative MRD detection was performed on 6 cases and revealed a positive rate of 100%. MRD detection was performed twice on 2 patients during preoperative neoadjuvant therapy. For the patient with constant allele frequencies detected throughout the treatment course, imaging showed tumor enlargement; While for another patient with a trend of reduction in allelic frequency, imaging showed tumor shrinkage and necrotic tumor tissue was observed in surgery one month later. These two patients had not recurred after surgery at the time of analysis. Post-surgery MRD detection were performed on 27 patients, of which 1 STS and 7 BTs were positive (30%, 8/27). Three of them confirmed recurrence by imaging at 12, 30, and 101 days after detection of positive MRD, respectively. However, there were still no imaging recurrence in the other patients so far, including the 5 remaining patients with positive MRD and 19 patients with negative MRD. Follow-up is still ongoing. Conclusions: MRD tests had been successfully performed in most of the sarcoma patients. Due to the heterogeneity of sarcomas, about 64% of mutated genes of sarcomas are unique individually, which may be more suitable for monitoring with tumor-informed MRD panel. Tumor-informed MRD could be used to predict the efficacy of preoperative neoadjuvant therapy and discover recurrence earlier than imaging in sarcoma.
Deep learning with whole slides images to predict histological response to neoadjuvant chemotherapy in patients with resectable high grade soft-tissue sarcomas: A multicenter study.
Authors: Adjadj Benjamin , Schutte Kathryn , Maussion Charles , Jean-Denis Myriam , Karanian Marie , Coindre Jean Michel , Italiano Antoine 
Published: June 2023

11512 Background: Two recent randomized trials have confirmed the potential benefit of neoadjuvant anthracycline-based chemotherapy in patients with high-grade soft-tissue sarcomas (STS) (Issels et al 2018, Gronchi et al 2017). However, as for adjuvant chemotherapy, the main issue with neoadjuvant treatment of STS patients is the identification of predictive factors of response to chemotherapy that could avoid for a majority of patients ineffective and potentially toxic treatment with impaired quality of life. Histological response, defined as the percentage of stainable tumor cells on the surgical specimen, has been shown to be a reliable surrogate for metastasis-free survival and overall survival in bone but also in soft-tissue sarcomas (Crombe et al JCO Clin Inf 2021). Developing a tool to help medical oncologists predict the potential benefit of neoadjuvant chemotherapy prior to starting the treatment would be of great value for precision medicine in sarcomas. To address this need, we propose a deep learning-based approach to predict histological response to neoadjuvant chemotherapy patients from routine histological whole slide images sampled at diagnosis. Methods: A cohort of 220 patients with high grade limb and trunk wall STS enrolled in the NEOSARCOMICS study (NCT02789384, sponsor: Institut Bergonié, Bordeaux, France) was used to train a model to predict the binarized histological response from diagnostic biopsies. Responders are defined by a histological response inferior or equal to 10%. Digitized hematoxylin/eosin slides were preprocessed to segment the tissue and decompose the image into patches of smaller resolution. Features were extracted from each patch using a Vision Transformer pretrained in a self-supervised fashion on histology slides. A Multiple Instance Learning model was trained on the resulting features to compute a prediction at the patient level. The algorithm was trained and validated through a 5-fold, 5-repeat cross-validation scheme. Finally, external validation is performed on an unseen cohort from Centre Léon Bérard to assess the robustness of the model. Results: To predict histological response to neoadjuvant chemotherapy, a model using only diagnostic biopsies achieved an AUC of 0.69 (95% confidence interval, 0.60-0.76). External validation is ongoing and shows promising preliminary results with an AUC of 0.67 (95% confidence interval with bootstrapping, 0.45-0.89). Conclusions: This multi-center study demonstrates that deep-learning models can accurately predict the histological response to neoadjuvant chemotherapy from routine histological whole slide images sampled at diagnosis. This model could be used as a pre-screening tool to improve patient selection for neoadjuvant chemotherapy in STS.
A phase II basket trial of dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART) SWOG S1609: The desmoid tumors (cohort 27).
Authors: Chae Young Kwang , Othus Megan , Patel Sandip Pravin , Powers Benjamin , Hsueh Chung-Tsen , Govindarajan Rangaswamy , Bucur Silvana Z. , Chung Liam Il-Young , McLeod Christine , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles David , Kurzrock Razelle 
Published: June 2023

11516 Background: Dual inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors is efficacious in many malignancies, but their potential role in numerous rare solid cancers is yet to be established. Desmoid tumors (DT; fibromatosis) are rare tumors of the soft tissue, and the mainstay of treatment is surgery (Richard Riedel, 2022). The utility of immunotherapy in this group of patients has not been explored. This study presents the first results of ipilimumab and nivolumab used in the DT cohort (#27) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint includes objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)). Secondary endpoints include progression-free survival (PFS), overall survival (OS), stable disease (SD) > 6 months, and toxicity. Results: Sixteen evaluable patients (median age 37) with desmoid tumors were analyzed. Location of the tumors are: 8, abdomen; 3, lower limb: 2, upper limb; 2, pelvis; and 1, neck. ORR was 18.8% with 3 patients attaining PR: 40% regression with ongoing duration of response (DoR) at over 30+ months; 83% regression (PFS 16 months); and 71% regression (PFS of 8.4 months). Of note, 3 patients had SD (3/16, 18.8%) with some shrinkage of the tumors and a durable response; 23% regression with PFS of 1820+ days; 6% regression with PFS of 902 days; 1% regression with PFS of 1147+ days. Overall clinical benefit rate (CBR; no progression > 6 months) was 62.5%. The median PFS was 17.9 months, 6-month PFS 69%, 1-year PFS 62%. All patients were alive at 1 years; median OS was not assessable as 14 patients are showing ongoing survival. The most common adverse events were fatigue (43.8%, n = 7), nausea (37.5%, n = 6), hypothyroidism (31.3%, n = 5), diarrhea, hyperthyroidism, headache, and adrenal insufficiency (25%, n = 4 each). There were 8 incidents (50%) of grade 3-4 adverse events. 7 adverse events led to discontinuation. There were no grade 5 adverse events. Conclusions: Ipilimumab plus nivolumab in treatment of desmoid tumors resulted in an ORR of 18.8% and CBR of 62.5% with durable responses seen. This is the first prospective study demonstrating efficacy of the combination in this rare disease. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in desmoid tumors are needed. Clinical trial information: NCT02834013 .
Results from phase I/II study of NY-ESO-1-specific TCR gene-transduced T cell therapy (TBI-1301, mipetresgene autoleucel) in patients with advanced synovial sarcoma.
Authors: Kawai Akira , Ishihara Mikiya , Nakamura Tomoki , Kitano Shigehisa , Iwata Shintaro , Takada Kohichi , Emori Makoto , Kato Koji , Endo Makoto , Matsumoto Yoshihiro , Kakunaga Shigeki , Sato Eiichi , Miyahara Yoshihiro , Morino Kunihiko , Tanaka Shinya , Takahashi Shuichi , Matsumine Akihiko , Kageyama Shinichi , Ueda Takafumi 
Published: June 2023

11558 Background: Synovial sarcoma is one of malignant soft tissue tumors with a poor prognosis. A cancer-testis antigen NY-ESO-1 is expressed in the tumors of 50-80% synovial sarcoma patients. The purpose of this study was to evaluate the safety and the efficacy of gene engineered autologous T cell product with NY-ESO-1 siTCR retroviral vector which expressed affinity-enhanced NY-ESO-1-specific TCR and siRNA to silence endogenous TCR (TBI-1301). Methods: This was an open label phase I/II study to evaluate safety, appearance of replication competent retrovirus (RCR), appearance of clonality, in vivo cell kinetics and clinical responses. TBI-1301 were manufactured from each subject’s leucocytes stimulated with anti-CD3 antibody and Retronectin and transduced with NY-ESO-1 siTCR retroviral vector. TBI-1301 was infused at split dose of 5 x 109 cells following cyclophosphamide treatment at 750 mg/m2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy. Results: Eight subjects were enrolled and treated with TBI-1301. The objective response rate was 50.0% with best overall partial response in 4 of 8 subjects according to RECIST v1.1/irRECIST and the median overall survival was 650 days. Cytokine release syndrome (CRS) occurred in 50.0% (4/8) and consisted of 1 subject with grade 1 CRS and 3 subjects with grade 2 CRS. All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid. No subjects had immune effector cell- associated neurotoxicity syndrome (ICANS). RCR and clonal dominance were not detected in any subjects throughout the study period. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325 .
Evaluation of hyperprogression in patients with sarcoma treated with targeted therapy and/or immunotherapy in early-phase clinical trials.
Authors: Alshibany Aisha , Al-Ezzi Esmail Mutahar , Gupta Abha A. , Salawu Abdulazeez , Watson Geoffrey Alan , Wang Lisa , Bedard Philippe L. , Spreafico Anna , Hansen Aaron Richard , Siu Lillian L. , Abdul Razak Albiruni Ryan 
Published: June 2023

11560 Background: Hyper-progressive disease (HPD) is an adverse outcome with acceleration of tumor growth, often accompanied by clinical deterioration. This phenomenon is described with immunotherapy (IT) but its incidence in sarcoma and/or in the context of targeted therapy (TT) remains unknown. Tumor growth rate (TGR) allows for dynamic evaluation of tumor volume change over time and may complement RECIST. We evaluated HPD in sarcoma patients (pts) treated in early-phase trials by assessing TGR and describing their subsequent clinical outcomes. Methods: We retrospectively reviewed medical records from advanced soft tissue sarcoma (STS) pts enrolled in early phase trials at the Princess Margaret Cancer Centre between January 2012 and December 2022. TGR was calculated based on tumor measurements taken at pre-baseline, baseline, and on-treatment CT scans. We used the Champiat formula (Clin Cancer Res 2017) to calculate TGR ratio. Primary objective was to describe the incidence of HPD, defined as a TGR ratio of > 50%. Secondary objective was to investigate the correlation between HPD with progression-free survival (PFS) and overall survival (OS). Results: We identified a total of 192 pts involved in STS early phase trials from 2012-2022. Most common histology was leiomyosarcoma seen in 72 pts. Eighty-four pts (43.8%) received TT, 75 (39%) pts received IT-based, and the rest had combined TT/IT regimens (n = 33, 17.2%). The incidence of HPD was 6.8% (n = 13), including IT-based (n = 9) and non-IT-based (n = 4) regimens. HPD was associated with a worse PFS, and OS compared to non-HPD pts (median PFS 1.6m vs 4.6m HR: 5.5, 95%CI 2.8-10.6, P < 0.001; median OS 5.5 vs 16.1 months; HR: 3.7, 95%CI: 2.0-7.1, P < 0.001). On multivariable analysis, only IT was significantly associated with HPD (OR 3.9, 95%CI: 1.1-13, P = 0.021). There was no association between HPD and new lesions or sarcoma histology subtype. Conclusions: HPD occurs in a small subset of sarcoma patients undergoing clinical trials with TT or IT. Exploring TGR provides clinically meaningful data as it pertains to HPD as it predicts OS and PFS in sarcoma patients undergoing early-phase clinical trials.