bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodality, online oncology learning resources: Meeting residents where they are—A pilot to create a new oncology curriculum.
Authors: King Jennifer , Pham Phillip , Khalid Ahmed Bilal , Sabra Mohamad , Schwartz Jennifer E. 
Published: June 2023

11035 Background: The Accreditation Council for Graduate Medical Education (ACGME) requires internal medicine residents to have access to different medical subspecialties, including hematology/oncology. While inpatient rotations in hematology/oncology have been associated with a decreased interest in a career in oncology, dedicated educational sessions have been shown to improve residents’ interest in the field. In recognition of different learning styles and modalities and the need for asynchronous delivery, we aimed to build an effective curriculum for oncology learners using interactive, multimodality, online learning tools and resources. Methods: Using the Canvas online learning management system, individual learning modules covering major cancer types were created. Each learning module consisted of a pre-survey assessing the learners’ evaluation of their own knowledge and comfort with the topic, a brief audio or video file covering high-yield information about the cancer type, interactive case-based questions reviewing and reinforcing the information, and a post-survey assessing the change in the learners’ evaluation of their knowledge and comfort in clinical application of the information. The pre- and post-surveys were rated on a 5-point Likert scale. Median values and interquartile ranges are reported. A one-sided t-test was used to compare responses. Results: Two fully completed learning modules have been created. The lung cancer module included a high-yield, 10-minute voice-over PowerPoint presentation followed by interactive, case-based questions. The breast cancer module used a high-yield, 10-minute podcast with an accompanying handout for notes followed by case-based interactive questions. Seven learners have completed both pre- and post-survey responses for comparison. Two were completed by PGY1, 4 by PGY2, and 1 by a PGY3 resident. Median rating of the learners’ knowledge of the specific cancer type increased from 2- Fair (1.5) on the pre-survey to 3- Neutral (1) after completing the learning module (p = 0.001). 100% of learners agreed or strongly agreed that their knowledge increased after completing the module. All 7 residents felt more comfortable with their clinical application of the cancer topic material after completing the module, median 2(1) on pre-survey vs. 3(0.5) on post-survey; p = 0.0004. Conclusions: The creation of online, multimodality learning resources has resulted in improvements in learners’ perceived knowledge and comfort with clinical application of oncology topics. Using learning science principles, this pilot project serves as the foundation for further innovative and interactive educational resources and modules created for oncology learners.
A pilot curriculum to transition from 2D to 3D image-guided brachytherapy: A preliminary needs assessment.
Authors: Ogunmuyiwa Joy , Aliyu Usman Malami , Joseph Adedayo , Adegboyega Bolanle Comfort , Balogun Onyinye 
Published: June 2023

11039 Background: Gynecologic cancers are one of the leading causes of death globally with a disproportionate burden of disease found in low to middle income countries (LMIC). Brachytherapy is often a necessary component in treatment management as it can deliver a high dose of radiation to the tumor while employing a steep dose fall off that spares the adjacent organs at risk. With 3D image guided brachytherapy (3D-IGBT), treatment planning utilizes volumetric images with the target volume and organs at risk contoured, reducing toxicity and improving outcomes when compared to 2D planar imaging. Despite this advantage, only a limited number of LMIC centers perform 3D-IGBT. Transitioning to 3D-IGBT requires considerable planning, resources, and training. The development of a multidisciplinary, computer-based training program to facilitate the transition to 3D-IGBT was identified as a priority of multiple Radiation Oncology departments in Nigeria. The aim of this preliminary needs assessment was to identify the necessary resources and anticipated barriers to development of a pilot training curriculum for the transition to 3D-IGBT. Methods: An anonymous, 16-question online survey was distributed to clinicians, physicists, radiation therapists, and staff within a Radiation Oncology department of a teaching hospital in Lagos, Nigeria. Results: In January 2023, 53 respondents completed the survey. Of the respondents, 36.5% were female and 63.5% were male. The average age was 37.5 (SD = 7.8). Clinical experience ranged from < 5 years (52.6%), 6-10 years (9.4%), to > 10 years (30.2%). Respondents included radiation therapists (28.8%), clinicians (27%), nurses (23.1%), and physicists (15.4%). Multiple barriers to implementation of 3D-IGBT were identified including lack of training (79.2%) or experience (58.5%), lack of financial investment (50.9%), and anticipated repair/replacement of equipment (41.5%). A majority of respondents identified staff training/education (66%) as critical to delivering 3D-IGBT. When asked about the curriculum components needed, most respondents believed that it should include plan review (96.2%), contour review (94.3%), and peer review of clinical cases (92.5%). Conclusions: Various areas of potential need were identified through this preliminary needs assessment, most notably, staff training. These findings suggest that there is an unmet need to further develop and implement a structured didactic and skills-based curriculum to transition from 2D to 3D-IGBT at these institutions. Identified focus areas including contour, peer, and plan review will help guide the refinement of this curriculum. These findings are an important first step in delivery of safe and efficacious 3D-IGBT in an LMIC.
Prognostic value of HER2-low status in breast cancer: A systematic review and meta-analysis.
Authors: Molinelli Chiara , Jacobs Flavia , Agostinetto Elisa , Marta Guilherme Nader , Ceppi Marcello , Bruzzone Marco , Blondeaux Eva , Schettini Francesco , Prat Aleix , Viale Giuseppe , Del Mastro Lucia , Lambertini Matteo , de Azambuja Evandro 
Published: June 2023

1104 Background: HER2-Low breast cancer (BC) has been recently identified as a new therapeutic target. However, it is unclear if HER2-Low status has an independent impact on prognosis, both in metastatic and early settings. Methods: A systematic literature research of PubMed, Cochrane and conference proceedings (ASCO meetings, SABCS and ESMO congress) up to December 8, 2022 was performed to identify studies comparing survival outcomes of patients affected by HER2-Low BC vs. HER2-zero BC. HER2-Low status was defined as immunohistochemistry score 1 + or 2+ without in situ hybridization amplification. Pooled hazard ratios (HRs) for survival endpoints in the metastatic [progression-free survival (PFS), overall survival (OS)] and in the early [disease free-survival (DFS) and OS] settings as well as their 95% confidence intervals (95%CI) were calculated using the random-effect model of Der Simonian and Laird. The above-mentioned endpoints were also assessed according to estrogen receptor (ER) status. Results: Among 1,916 identified records, 42 studies including 1,797,377 patients were eligible for this analysis. We show the pooled HRs in the overall population and specific subgroups. In the early setting, HER2-Low status was associated with significant improved DFS (HR 0.86, 95%CI 0.79-0.92, p<0.001) and OS (HR 0.84, 95%CI 0.77-0.92, p<0.001) when compared to HER2-zero status. Improved OS was observed in subgroup analysis for both ER-positive and ER-negative HER2-Low populations, while DFS improvement was observed only in the ER-positive subgroup. Similarly, in the metastatic setting, patients affected by HER2-Low BC showed better OS when compared to those with HER2-zero BC (HR 0.94, 95%CI 0.89-0.98, p=0.008). HER2-Low metastatic BC was associated with significant improvement in OS compared to HER2-zero BC also in ER-positive and ER-negative subgroups. No significant differences were found in terms of PFS. Conclusions: Compared with HER2-zero status, HER2-Low status appears to be associated with an increased OS both in the advanced and early settings, regardless of hormone-receptor expression. [Table: see text]
Safety and clinical activity of TTI-621 in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma: Results from the low-dose expansion cohort.
Authors: Movva Sujana , Druta Mihaela , Davis Lara E. , Monga Varun , Milhem Mohammed M. , Bailey Howard Harry , Chugh Rashmi , Bruns Ingmar , Allgood Victoria E , Chawla Sant P. 
Published: June 2023

11508 Background: TTI-621 is a recombinant fusion protein combining the Fc region of human IgG1 with a fragment of human SIRPα, designed as a decoy receptor for CD47 on tumor cells to interrupt CD47-SIRPα signaling and promote macrophage-mediated phagocytosis of tumor cells as well as activation of NK cells. Preclinical studies suggest TTI-621 may enhance the response to doxorubicin in macrophage-rich tumors that express CD47, such as leiomyosarcoma (LMS). A phase 1/2 dose escalation study with high- and low-dose expansion cohorts evaluating TTI-621 + doxorubicin in patients (pts) with advanced LMS is ongoing (NCT04996004); results from the low-dose expansion cohort are presented. Methods: This open-label study enrolled anthracycline-naïve pts aged ≥18 y with evaluable unresectable or metastatic high-grade LMS and ≤1 prior line of therapy for advanced disease. Pts in the low-dose expansion cohort received TTI-621 0.2 mg/kg on Days 1 and 8 in combination with doxorubicin 75 mg/m2 on Day 1 of 21-day cycles for a maximum 6 cycles, followed by TTI-621 monotherapy on Days 1 and 15 of 28-day cycles until objective disease progression. Primary objectives for the expansion phase were evaluation of safety and investigation of clinical activity via assessment of overall response and clinical benefit rates as defined by RECIST v1.1 criteria. Results: At data cut-off (Oct 3, 2022), 23 pts were evaluable for safety and 20 for clinical response. In the safety population, 39% had received prior treatment for advanced disease. Two pts (9%) experienced Grade ≥3 AE assessed as related to TTI-621 treatment: pancreatitis (n = 1, 4%) and platelet count decreased (n = 1, 4%). Seven pts (30%) experienced Grade ≥3 AE related to the combination of TTI-621 and doxorubicin, including two pts (9%) each with platelet count decreased and white blood cell count decreased and three pts (13%) with neutrophil count decreased. Grade ≥3 doxorubicin-related AEs were more common (n = 17, 74%); most frequent were neutrophil count decreased (n = 8; 35%), white blood cell count decreased (n = 7; 30%), and neutropenia (n = 6; 26%). One pt experienced an infusion-related reaction (Grade 1 chills) assessed as related to TTI-621. No pts attained complete response, but one pt had a complete resolution of all target lesions. Five pts (25%) attained partial response for an overall response rate of 25%; 11 pts (55%) attained stable disease for a disease control rate of 80%. Conclusions: Addition of TTI-621 to doxorubicin showed promising clinical activity and a favorable safety profile among pts with advanced LMS, including those with prolonged exposure to TTI-621 ( > 360 d). Clinical trial information: NCT04996004 .
A pilot study of lenvatinib plus pembrolizumab in patients with advanced sarcoma.
Authors: Movva Sujana , Avutu Viswatej , Chi Ping , Dickson Mark Andrew , Gounder Mrinal M. , Kelly Ciara Marie , Keohan Mary Louise , Meyers Paul A. , Cohen Seth M. , Hensley Martee Leigh , Konner Jason A. , Schram Alison M. , Lefkowitz Robert A , Erinjeri Joseph Patrick , Qin Li-Xuan , Salcito Tiffany , Seier Kenneth , Tap William D. , D'Angelo Sandra P. 
Published: June 2023

11517 Background: New treatment options are needed for sarcomas. Lenvatinib (L) is an oral, multi-tyrosine kinase inhibitor with significant inhibitory activity against VEGF receptor (VEFGR) 1-3, FGF receptor (FGFR) 1-3, KIT, platelet-derived growth factor receptor (PDGFR) alpha/beta, and RET. Experimental models suggest that L can favorably alter the tumor immune environment, and the combination of L and pembrolizumab (P) has proven to be synergistic and effective across multiple solid tumor types, providing rationale for this study. Methods: This is a pilot study evaluating the efficacy of L and P in select sarcomas. Patients who had at least 1 prior regimen but ≤ 3 were enrolled into one of five cohorts (n = 10 each) A: leiomyosarcoma (LMS); B: undifferentiated pleomorphic sarcoma (UPS); C: angiosarcoma and epithelioid hemangioendothelioma (EHE); D: synovial sarcoma (SS) and malignant peripheral nerve sheath tumor (MPNST); and E: osteosarcoma (OS) and chondrosarcoma (CS). Patients were treated with an initial 2-week run-in of L 20 mg orally daily. Subsequently, P was administered at 200 mg IV every 21 days. The primary endpoint for each cohort was the best objective response rate (ORR) documented by RECIST v1.1 by 27 weeks. The combination was considered worthy of further study if 2 or more responses were observed in a cohort. Secondary endpoints included progression-free survival (PFS), overall survival, duration of response, and safety of the combination. Archival tissue and on-treatment biopsies were collected. Results: As of January 31st, 2023, cohorts A, D and E have completed accrual. The best response in the LMS cohort was stable disease (SD). In cohort D there were 3 partial responses (PR): 2 SS; 1 radiation associated high grade MPNST. In cohort E one of 6 patients with OS had a PR. To date, of the 6 patients with angiosarcoma, there was 1 PR in a patient with adrenal primary that occurred after the prespecified 27-week timepoint. One of 5 evaluable patients in Cohort B had a PR. Among the 44 patients evaluable for safety, most common AEs were hypertension (56.8%), diarrhea (45.5%), proteinuria (45.5%), fatigue (40.9%), headache (36.4%) and nausea (36.4%). Most common ≥ grade 3 AEs were hypertension (13.6%), dyspnea (6.8%), non-cardiac chest pain (6.8%), syncope (6.8%). Conclusions: A signal of activity was noted in this pilot study for patients with OS, MPNST, angiosarcoma and SS. In the LMS cohort, there were no responses, and PFS was poor. Enrollment to cohorts B and C is ongoing. Clinical trial information: NCT04784247 . [Table: see text]
Two schedules of vincristine, irinotecan and temozolomide (VIT) for patients with relapsed or refractory Ewing sarcoma: A randomized controlled phase 2 trial.
Authors: Xu Jie 
Published: June 2023

11525 Background: Vincristine, irinotecan and temozolomide (VIT) has provided an effective regimen in relapsed or refractory Ewing sarcoma patients. Optimal dose schedule of VIT is still undefined. Methods: We did this phase 2 randomized controlled trial and included patients with relapsed or refractory Ewing sarcoma. They were randomly assigned (1:1) by random number table method to either shorter dx5 schedule (Irinotecan 50mg/m2/d D1-5, Vincristine 1.4mg/m2 D1) or protracted dx5x2 schedule (Irinotecan 20mg/m2/d D1-5,8-12, Vincristine 1.4mg/m2 D1,8) together with a fixed dose of temozolomide (100mg/m2/d D1-5) in both groups. Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to eight cycles. The primary endpoint was objective response rate at 12 weeks (ORR12w). The secondary endpoint was progression-free survival (PFS), overall survival (OS) and safety. The study was powered to detect a 30% improvement in the response rate from 20% of dx5 schedule to 50% of dx5x2 schedule (α = 0.1, 1-β = 0.9, one-sided test favoring dx5x2 schedule since the only difference of clinical importance was an improved response with the inconvenient schedule of dx5x2). A sample size of 30 patients per group (60 randomly assigned patients) was required to detect a significant improvement in ORR12w. Results: Between May 21, 2020, and August 8, 2022, 24 patients were randomly assigned to dx5 schedule while 22 to dx5x2 schedule, respectively. Median follow-up was 10.7 months (IQR 9.7-13.9) in the dx5 group and 8.3 months (IQR 4.4-15.3) in the dx5x2 group. ORR12w was lower in dx5 group than in dx5x2 group (5 [20.8%] of 24 patients vs 12 [54.5%] of 22; p = 0.019). There was no significant difference in PFS between the two groups (median PFS 2.3 months [95% CI 0.0-4.7] in dx5 group vs 4.3 months [2.7-6.0] in dx5x2 group; hazard ratio [HR] 0.956 [95% CI 0.84-1.09]; p = 0.434). Also, there was no significant difference in OS (median OS 14.8 months [95% CI 12.0-17.6] vs 12.8 months [95% CI 6.9-18.7]; HR 0.957 [95% CI 0.81-1.12]; p = 0.594). Patients in dx5 schedule reported more grade 3 and 4 adverse events (AEs) than dx5x2 schedule, including diarrhea/abdominal pain (23[23.7%] of 97 courses vs 8[8.4%] of 95 courses, p = 0.005), vomiting/nausea (6[6.2%] vs 1[1.15%], p = 0.035). Other common grade 3 and 4 AE ( > 5%) were similar between two schedules (p > 0.05), including fatigue (24[24.7%] vs 14[14.7%]), leukopenia (6[6.2%] vs 8[8.4%]), neutropenia (5[5.2%] vs8 [8.4%]), and anemia (5[5.2%] vs 7[7.4%]). Unfortunately, the isolation policy of COVID-19 significantly restricted the speed of recruiting and the sponsor stopped following support to our study. Conclusions: Protracted dx5x2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter dx5 VIT schedule in patients with relapsed or refractory Ewing sarcoma. Clinical trial information: NCT03359005 .
ALMB-0168, a novel Cx43 hemichannel agonist monoclonal antibody, for metastatic or unresectable osteosarcoma after standard chemotherapy: A multicenter, open-label, single-arm, phase 1 study.
Authors: Shen Jingnan , Guo Wei , Wang Jin , Xie Xianbiao , Xie Lu , Xu Jie , Jing Chen , Lin Jianhua , Li Xianan , Zhou Yong , Wang Guowen , Zhang Xiaojing , Weitao Yao , Dong Yang , Ye Zhaoming , Wang Li , Zeng Yanyan , Wu Yongyong , Yang Xiugao , Zhang Yanfeng 
Published: June 2023

11530 Background: The treatment of metastatic or unresectable osteosarcoma after standard chemotherapy remains a significant clinical challenge. Connexin 43 (Cx43) hemichannel has been suggested to be a key regulator of bone homeostasis and represents a new target for bone and breast cancer. ALMB-0168, a first-in-class therapeutic antibody agonist for Cx43 hemichannel, has been shown to suppress the growth and migration of osteosarcoma and breast cancer bone metastases in preclinical studies. Methods: Patients ≥16 years with histologically confirmed osteosarcoma who progressed after standard chemotherapy were eligible. This study consists of accelerated titration followed by a 3+3 design with 7 planned ALMB-0168 dose levels (1, 3, 6, 12, 18, 24, and 30 mg/kg) administered intravenously once every 3 weeks and then dose expansion at the potential recommended phase 2 dose (RP2D). Primary endpoints are safety and tolerability. Adverse events are rated according to the NCI CTCAE v5.0. Key secondary endpoints are overall response rate (ORR) and disease control rate (DCR) assessed using RECIST v1.1. Results: As of August 21, 2022, 14 patients (10 males, 4 females) with median age 27.5 years (range 16–38 years) were enrolled; ECOG PS was 0 in 7 patients (50.0%), 1 in 6 patients (42.9%) and 2 in 1 patient (7.1%). 5 patients received ≥2 prior lines of therapy. Six dose levels (1-24 mg/kg) have been completed in this ongoing study with no dose-limiting toxicities reported. Treatment related adverse events (TRAEs) of any grade occurred in 10 (71.4%) patients and were Grade 3 in 1 patient (infectious pneumonia); no events were Grade 4 or 5. Common TRAEs ( > 10%) were proteinuria (21.4%), anemia (21.4%), hematuria (14.3%), and increased aspartate aminotransferase (14.3%). No Cx43-related cardiac events or severe hepatic events were observed. A total of 13 patients were evaluable for response. ORR was 15.4% (2/13, 95% CI: 1.9–45.5%), including 2 partial responses (PR), 1 patient each at 6 mg/kg and 18 mg/kg. The patient at 6 mg/kg, who had ≥3 prior lines of therapy and lung metastases, achieved durable disease control with stable disease (SD) for 33 weeks followed by PR for 8+ weeks (at the time of analysis). The DCR was 53.8% (7/13, 95% CI: 25.1–80.8%) with 2 PRs and 5 SDs. Conclusions: ALMB-0168 demonstrated encouraging efficacy and tolerable safety in patients with metastatic or unresectable osteosarcoma after standard chemotherapy in a phase 1 dose-escalation trial. Dose escalation is ongoing and dose expansion will start at the potential RP2D levels. Clinical trial information: NCT04886765 .
Fluorine-18 fluorodeoxyglucose (18FDG)-uptake assessment of PDGFRA mutant gastrointestinal stromal tumors (GIST): A retrospective multicenter Italian study.
Authors: Nigro Maria Concetta , Marchetti Andrea , Fumagalli Elena , De Luca Ida , Bertuzzi Alexia Francesca , Grimaudo Maria Susanna , Grignani Giovanni , D'Ambrosio Lorenzo , Merlini Alessandra , Carreca Ignazio , Incorvaia Lorena , Dimino Alessandra , Gasperoni Silvia , Vincenzi Bruno , Pantaleo Maria A. , Nannini Margherita 
Published: June 2023

11539 Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile. Although functional imaging with 18FDG-PET plays a proven role in GIST, especially in early assessment tumor response, less is known about 18FDG-uptake according to the GIST molecular subtypes. Taking into account of clinical and molecular features of D842V mutant GIST, we assumed that this subset of GIST could also have a different 18FDG-uptake. Therefore, the aim of the present study has been to investigate the degree of FDG uptake of PDGFRA mutant GIST, focusing on D842V ones, in order to better define the role of functional imaging in this rare and peculiar subset of GIST. Methods: Patients with PDGFRA mutant GIST underwent 18FDG-PET were retrospectively included from seven GIST Italian reference centers. Data on maximum standardized uptake (SUVmax) value of primary tumor or metastatic disease were collected. Results: 71 patients have been included: 37 (55.1%) with D842V PDGFRA mutant GIST (group A) and 34 (47.9%) with PDGFRA non-D842V mutant GIST (group B). Additionally, 30 patients with exon 11 KIT mutant GIST have been included, as control (group C). SUVmax values were obtained from primary tumor and metastatic lesions in 55 (54,4%) and 46 (45,6%) patients, respectively. Considering the whole population of 101 patients, the global median SUVmax was 3,7 (IQR 0-9.1), while the median SUVmax for group A, B, and C was 0, 3.6, and 10.4, respectively. The median SUVmax of PDGFRA mutant GIST was significantly lower than the median value of exon 11 KIT mutant GIST (p < 0.001). Notably, median 18FDG-uptake was significantly lower in D842V PDGFRA mutant GIST compared to PDGFRA non-D842V mutant ones (p = 0.021). Conclusions: PDGFRA D842V-mutant GIST present an overall lower 18FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with 18FDG-PET in this subset of GIST is limited. Finally, the prognostic value of the 18FDG-uptake degree within all PDGFRA mutant GIST will be investigated in the future.