bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of AK104 (an anti-PD1 and anti-CTLA4 bispecific antibody) combined with standard therapy for the first-line treatment of persistent, recurrent, or metastatic cervical cancer (R/M CC).
Authors: Wang Jing , Lou Hanmei , Cai Hong-Bing , Huang Xin , Li Guiling , Wang Li , Liu Ting , Liu Wei , Li Baiyong , Xia Yu 
Published: June 2022

106 Background: Current first-line standard therapy (SOC) for R/M CC is platinum-based chemotherapy +/- bevacizumab (bev). AK104 monotherapy has shown promising efficacy and tolerable toxicity in pretreated R/M CC (NCT04380805). In this study, we report the efficacy and safety of AK104 combined with SOC for the first-line treatment of R/M CC (NCT04868708). Methods: The multicenter, open-label, phase II study enrolled R/M CC pts without previous systemic therapy. Eligible pathological types were squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. Pts were assigned to 3 cohorts (A-15/A-10: AK104 15/10 mg/kg + PTX 175mg/m2 + DDP 50 mg/m2/CBP AUC 5, q3w; B-10: AK104 10 mg/kg + PTX 175 mg/m2 + DDP 50 mg/m2/CBP AUC 5 + bev 15 mg/kg, q3w). All pts received AK104 until PD or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included ORR, PFS per RECIST1.1, and OS, etc. Results: 45 pts were enrolled at 6 centers from Jun 3, 2021, to Nov 5, 2021. As of Jan 10, 2022, we assessed safety in all pts and efficacy in pts with at least one tumor assessment result. TRAEs of any grade occurred in 43 (95.6%) pts. Grade ≥3 TRAEs occurred in 23 (51.1%) pts. The most common TRAEs were anemia (55.6%), white blood cell count decreased (46.7%), rash (24.4%), and hypoesthesia (24.4%). The most common grade ≥ 3 TRAEs were anemia (15.6%), white blood cell count decreased (11.1%), neutrophil count decreased (8.9%), and platelet count decreased (8.9%). TRSAE occurred in 17 (37.8%) pts. IrAEs of any grade, assessed by INV, occurred in 24 (53.3%) pts. Grade ≥ 3 irAE occurred in 8 (17.8%) pts. One death due to hemorrhagic shock occurred in cohort B-10 and was judged as treatment-related. ORR were 73.3% (11/15) for A-15, 68.8% (11/16) for A-10, 92.3% (12/13) for B-10, respectively. The response to the treatment was favorable regardless of CPS (Table). PFS or OS data are not mature by cut-off date. Conclusions: AK104 combined with standard therapy was well tolerated, with encouraging antitumor activity in pts with R/M CC. Meanwhile, long-term safety evaluation still needs following up. A phase III trial is ongoing to evaluate the efficacy of AK104 plus standard therapy in first-line treatment for R/M CC (NCT04982237). Clinical trial information: NCT04868708. [Table: see text]
Clinical value of next-generation sequencing in endocrine therapy for advanced hormone receptor–positive/HER2-negative breast cancer.
Authors: Lv Dan , Liu Binliang , Lan Bo , Li Lixi , Sun Xiaoying , Ma Fei 
Published: June 2022

1062 Background: Acquired gene mutation is a major mechanism of resistance to endocrine therapy in hormone receptor (HR)-positive advanced breast cancer. Circulating tumor DNA (ctDNA) facilitates the current assessment of the genomic profile in patients with advanced cancer. We performed this clinical trial to determine the landscape of gene mutation before endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. Methods: We conducted an open-label, single-center, multicohort, prospective study. Patients were women with pathologically and immunohistochemically confirmed HR-positive/HER-2-negative patients with advanced breast cancer. Patients relapsed during or after adjuvant endocrine therapy or progressed after completing at least one previous line of treatment for advanced breast cancer. Patients were assigned to four parallel treatment cohortsmatched to mutations identified in ctDNA: 1) cohort A comprised patients with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 2) cohort B comprised patients with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 3) cohort C comprised patients with HER2 mutations, preferred pyrotinib combined with endocrine therapy; 4) cohort D comprised patients with no significant gene mutation, making treatment plan according to the actual clinical situation. If more than one mutation was identified, the priority of entry is cohorts C, cohorts A and cohort B. In the A-D cohort, patients who obey the treatment plan are the compliance group, and patients who do not obey the treatment plan are the violation group. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS). Results: A total of 113 patients underwent NGS detection of ctDNA, and 84 patients were enrolled in the study. In all cohorts, combined median PFS was 4.9 months, and the median PFS in the compliance group was 3.0 months longer than in the violation group (6.03 vs 3.03 months, p = 0.0222, HR = 0.5743, 95%CI 0.3273-1.007). In cohort C, the median PFS was 11.1 months in the compliance group and 2.22 months in the violation group (p = 0.0067, HR = 0.1980, 95%CI 0.032-1.22). There was no significant difference in the median PFS between patients with and without compliance with the treatment protocol in cohort A and cohort B (p = 0.5054 and 0.7325, respectively). Conclusions: The study suggested that ctDNA detection may guide the optimal endocrine therapy strategy for patients with advanced breast cancer and achieve the benefit of progression free survival. NGS detection might distinguish patients with HER2 mutation and provide new treatment strategies. Clinical trial information: NCT03786575.
Real-world treatment patterns and outcomes among patients (pts) with second-line (2L) and third-line (3L) metastatic triple-negative breast cancer (mTNBC) in England using the Cancer Analysis System (CAS).
Authors: Chang Lawrence , Hall Peter S. , Preger Luciana , Sjekloca Nikoleta , Bergamaco Estevan , Broe Anne , Petrova Plamena , Berg Paul , Reich Adam , Pawar Neha , Gharaibeh Mahdi 
Published: June 2022

1075 Background: TNBC is the most aggressive type of breast cancer due to rapid growth, metastasis, and recurrence post-treatment. This study aimed to assess real-world treatment patterns and survival of pts with mTNBC who received 2L and 3L therapy in England and report OS and PFS of pts receiving 2L therapies stratified by treatment-free interval from the curative setting. Methods: This retrospective study using the CAS database, included pts with mTNBC who received at least three systemic treatments (at least two in metastatic setting) for TNBC during the years 2012 to 2020. Cohort2L included pts with initial early-stage BC diagnosis and treatment (at least two systemic treatments prior to 2L). Cohort3L included pts initially diagnosed with either early-stage TNBC, or de novo advanced TNBC (at least two systemic treatments prior to 3L). The two cohorts are not mutually exclusive. The study outcomes were stratified by cohort (Cohort2L and Cohort3L) and treatment-free interval (<12 m versus ≥12 m from end of curative treatment to start of 1L treatment, Cohort2L only). Kaplan-Meier methods estimated progression-free survival (PFS) and overall survival (OS). PFS was proxied by ‘Time to treatment discontinuation or death’ (TTDD). Log-rank tests compared the distribution of OS and PFS for 2L stratified by treatment-free interval (<12 m versus ≥12 m). Results: Cohort2L included 606 pts and Cohort3L included 374 pts. Tumor morphology was similar across Cohorts. Pts at 3L had worse ECOG performance score compared to 2L, and more pts with de novo advanced TNBC had brain metastasis at any point after diagnosis than pts diagnosed with early-stage TNBC. Regimens at 2L for Cohort2L included capecitabine (32%), eribulin (16%), carboplatin and gemcitabine in combination (12%), and paclitaxel (10%). A similar distribution was seen for Cohort3L. Regimens at 3L (Cohort3L only), included eribulin (38%), capecitabine (16%), and paclitaxel (13%). Stratifying Cohort2L by treatment-free interval did not exhibit significant differences in PFS nor OS by log rank tests (Table). Conclusions: This nationwide study, in England, accentuates the significant unmet need in 2L and 3L therapy for mTNBC highlighted by the poor prognosis. The stratification by prior treatment-free interval from curative setting did not show a difference in OS or PFS for patients receiving 2L treatment. [Table: see text]
Comprehensive whole-exome and transcriptome profiling to identify actionable alterations associated with response to PARP inhibitors in breast cancer.
Authors: Dombrowski Susan M. , Udhane Sameer S. , Basu Gargi D. , Hall David W. , Hoag Jess W. , Alyaqoub Fadel S. , Noel Pawan , Szelinger Szabolcs , Wang Min , Ozols Audrey A. , LoBello Janine R. , Thakkar Snehal Govind , Baehner Frederick L. , O'Shaughnessy Joyce 
Published: June 2022

1096 Background: The use of targeted therapies identified using genetic and genomic approaches is now routine in breast cancer (BC). In this clinical lab experience study the frequency of actionable somatic alterations in DNA repair pathway genes associated with the use of PARP inhibitors (PARPi) is described. Methods: BC samples were sequenced with the Oncomap ExTra assay, which uses whole-exome DNA sequencing with germline subtraction to detect somatic single base substitutions, indels, and copy number alterations, and RNA sequencing to detect gene fusions. Clinically actionable alterations were defined as associated with FDA approved drugs or clinical trial enrollment. Here, the focus is on 49 repair genes associated with PARPi response: ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, EPCAM, ERCC1/2/3/4/5, FANCA/C/D2/E/F/G/I/L/M, MLH1, MRE11A, MSH2/6, MUTYH, NBN, PALB2, PMS2, PPP2R2A, PTEN, RAD21/50/51/51B/51C/51D/52/54L, XRCC1/2/3. Results: Of 1103 BCs, 246 (22.3%) had mutations in repair genes; 69 (6.3%) were in BRCA1/2. Repair gene mutations were less common in HER2+ cancers (n=27, 14.3%) compared to HR+ HER2- (n=156, 23.9%) or TN cancers (n=49, 26.1%) (p<0.01). Across subtypes, the top four most commonly mutated of the repair genes were PTEN (27.2%), ARID1A (22.8%), BRCA2 (14.2%), and BRCA1 (14.2%); 33 cancers (13.4%) had mutations in multiple (≥2) repair genes. For the 69 cancers with BRCA1/2 mutations, 11 (15.9%) carried other repair gene mutations (9 of 35 BRCA1; 3 of 35 BRCA2). RNA sequencing found 19 fusions in repair genes in 17 patients (1.5%); CDK12 was involved in 13 (68.4%), and RAD51C in 3 (15.8%). Fusion incidence was more frequent in HER2+ cancers (p<0.01) (Table). Conclusions: PARPi therapy is FDA approved for HER2- germline BRCA1/2 mutated BC patients. Recent evidence suggests somatic BRCA1/2 mutations predict PARPi benefit (Tung, NM. J Clin Oncol 2020). In addition to BRCA1/2 alterations, our study also highlights the importance of alterations in other DNA repair genes associated with response to PARPi. Trials are ongoing to determine if these genes predict for PARPi benefit.[Table: see text]
A collaborative model for continuing medical education: Impact of a distance learning curriculum for existing radiation oncology centers in Africa and Latin America.
Authors: Balbach Meridith Leigh , Neely Grantly , Yorke Afua Adutwumwaa , Medina Evangelina Figueroa , Paly Jonathan Judd , Shulman Rebecca Maria , Cutrer William B. , Benjamin Li 
Published: June 2022

11007 Background: We aimed to evaluate the outcomes and generalizability of a distance learning curriculum on intensity modulated radiotherapy (IMRT), a course developed for radiotherapy clinics across Africa and Latin America (LATAM) at no cost, as measured by a knowledge-based multiple-choice exam, learner self-evaluation, and open-ended feedback. Methods: Following needs identification studies, a curriculum entitled “IMRT 2.0” was created for an audience that included medical physicists, radiation oncologists, radiation therapists, and trainees. Volunteer educators delivered 27 hour-long sessions 1-2 times weekly for four months using video conferencing to African and LATAM programs in English and Spanish, respectively. Recordings and educational materials were shared following each session. Pre- and post-course multiple choice examinations were administered to LATAM participants, and pre- and post-course Likert scale self-evaluation and open-ended feedback were collected for both programs. Paired sample t-tests and chi-squared tests were performed for all available paired quantitative and categorical data, respectively. Pearson correlation coefficient, multivariate linear regression, and spline regression models were used to explore impact of course attendance on outcomes. Results: 25 centers across Africa (12 + 1 sister institution in Pakistan) and LATAM (12) were recruited, the majority (92%) of which were recently transitioning or planning to transition to IMRT, yielding a total of 332 enrolled participants. 27 sessions were delivered with a mean of 44 (std dev 22.5) and 85 (std dev 25.4) participants per session for the African and LATAM programs, respectively. Paired pre- and post-course data demonstrated significant improvement in both knowledge (n = 51, p <.001) and overall self-confidence (n = 85, p <.001). Synchronous participation did not predict greater score improvement or increase in self-confidence. Thematic analysis suggests that participants found great value in this course and look forward to future learning. Conclusions: A volunteer-driven course on IMRT is generalizable across regions in different languages and serves as an effective hub to arm participating centers with the knowledge and confidence they need to enhance patient care at their institutions. This benefit may propagate as participants become the next generation of trainers. Other fields and specialties aiming to reduce global health care disparities through training efforts could consider adopting this approach.
Implementation and efficacy of a fellow-led, case-based noon lecture series.
Authors: Dickerson James , Myall Nathaniel James , Roy Mohana , Johnson Tyler Paul 
Published: June 2022

11011 Background: For new fellows, learning clinical oncology represents an enormous challenge. Few data support specific didactic approaches. The senior author (TPJ) developed a novel curriculum, emphasizing deliberate practice as part of a design grounded in Ericsson’s “expert performance approach”. These noon conferences are case based with a focus on key clinical trials and NCCN guidelines. In comparison to didactics given directly by faculty, these conferences are primarily presented by a senior teaching fellow with an invited faculty member adding additional commentary as an “expert discussant”. We surveyed fellows to assess perception of efficacy and also created a board style test to evaluate knowledge gains. Methods: The curriculum began in 2020. After one year, we surveyed fellows with a five-point likert scale survey to quantify their perception of the curriculum. In 2022, we created a pair of 18-question lung cancer specific board style tests for the five teaching sessions on lung cancer. Prior to the first conference, the pre-test was sent to fellows electronically; after the final lecture the other 18-question test was sent out. Differences in the overall cohort’s test score were examined via a paired student t-test. Results: On the 2021 survey, 59% of fellows responded (17 of 29). Of the respondents, 83% attended at least half of the lectures (14 of 17). When asked to compare this conference series to traditional lecture-based series, 59% (10 of 17) agreed with the statement that "this series is one of the very best I've encountered" and all said it was at least “better than average.” 94% of respondents (16 of 17) said the series equipped them for clinical practice to either a “significant” or “remarkable” degree. 94% of respondents (16 of 17) agreed the conferences helped them learn to “think like oncologists.” For the five session lung cancer block, fellows reported attending an average of 3.6 ± 1.4 sessions (n = 13). On the 18-question pre-test (n = 19), the average score ± one standard deviation was 73% ± 15%. For the post-test (n = 13), the average was 68% ± 17% (p = 0.48). Conclusions: We developed a novel curriculum to replace traditional didactics. Fellows perceived the curriculum to be exceptionally strong as compared to traditional lecture series, felt it prepared them well for practice, and said it taught them to think like oncologists. Pre/post knowledge assessments did not show an improvement in knowledge. Distribution to larger numbers of fellows–especially early learners–may better power a study to detect improvements in learning.
Factors associated with altmetric attention scores for randomized phase III cancer clinical trials.
Authors: Rooney Michael Kevin , Ludmir Ethan B. , Fuller Clifton Dave , Warner Jeremy Lyle 
Published: June 2022

11014 Background: The rise of the internet and social media has created new opportunities for the rapid sharing of scientific findings among professional and public communities. Altmetric Attention Scores (Altmetrics) are real-time measures of scientific impact and attention through various public outlets, including news, blogs, and social media. Distributions and patterns of Almetrics for high-impact clinical cancer research remain under-reported. Our goal was to describe the relationship between Altmetrics and other characteristics of published trials. Methods: We identified all two-arm superiority phase III cancer randomized controlled trials (RCTs) with a publication date between 2015-2020 from HemOnc.org. For included trials, we tabulated the followed the data: Altmetric score as of February 11, 2022; positive study (yes/no); FDA registration trial (yes/no); primary endpoint (categorized as overall survival (OS), progression-free survival (PFS), event-free/disease-free survival (EFS/DFS), or other); journal tier (defined as tier 1: NEJM, Lancet, JAMA; tier 2: JCO, Blood, Lancet Oncology, JAMA Oncology, Annals of Oncology or Tier 3: other). Univariable testing was performed with Pearson correlation, Wilcoxon rank sum, and Kruskal-Wallis testing to identify associations between predictor variables and Altmetrics. For factors with significant univariable associations, we generated a multiple linear regression model to identify clinical trial factors predictive of Altmetric attention scores, with alpha = 0.05 defining statistical significance. Results: Of 673 publications identified per inclusion/exclusion criteria, Altmetric scores were found for 638 (95%). The median score was 38.9 (IQR 12.4-126.7) – well above the 95th percentile for all Altmetric scores. On univariable testing, positive studies (P < 0.001), registration trials (P < 0.001), those published in tier 1 journals (P < 0.001), and trials with primary endpoint of OS (P = 0.002) were associated with increased Altmetric scores. On multivariable testing, positive studies (P = 0.006), registration trials (P < 0.001), studies published tier 1 journals (P < 0.001), and those reporting on OS (P = 0.03) persisted as significantly associated with increased engagement as measured by Altmetric scores. Conclusions: Social media and other online platforms represent an increasingly important avenue for the sharing of scientific and medical research. In this cross-sectional observational study, we found that certain characteristics of cancer clinical trials and publications are predictive of impact as measured by Altmetric scores. Specifically, positive registration trials published in traditionally defined high-impact journals and those reporting on OS as a primary endpoint tend to have the greatest Altmetric attention scores. The significance and consequences of these relationships warrant further investigation.
Impact of structured debriefing sessions on residents rotating on inpatient oncology.
Authors: Dalal Hina , Thilges Sarah , Mumby Patricia B. , Chervinko Nazzara , Girardi Ellen , Lo Shelly S. 
Published: June 2022

11018 Background: Participating in end-of-life (EOL) care may lead to physician distress and burnout. Residents rotating on inpatient oncology services often care for patients and families nearing the EOL. There is no standardized resident training for EOL care nor are there standardized methods to assist with resultant emotional distress. Studies have demonstrated that residents on hematology/oncology rotations experience acute empathy decline, which can lead to cynicism and depersonalization, contributing to burnout (McFarland, 2016). Our objective was to prospectively evaluate the impact of a structured debriefing session during a 4-week inpatient oncology rotation on residents' concerns about death and rotation satisfaction. Methods: During week 1, residents completed a 10-item Concerns about Dying (CAD) instrument (Mozer, 2004). During week 3, residents participated in a structured 60-minute debriefing session with a clinical psychologist or licensed social worker specializing in hematology-oncology. During week 4, residents completed the CAD and an end-of-rotation self-assessment. Results: 58 individual residents rotated through inpatient oncology at Loyola University Medical Center from 7/2020 – 1/2022. 15 residents were excluded as they did not complete both the pre and post surveys. Trainees had a lower CAD score at the end of their oncology rotation, indicating a more positive attitude towards death and dying. PGY1s had the greatest decrease in CAD score over 4 weeks. Anxiety (70%), relief (70%), satisfaction/pride (63%) and sadness (58%) were the most common emotions residents felt while providing EOL care. 42/43 (98%) residents were comfortable discussing EOL topics with a licensed counselor and 40/43 (93%) felt the debriefing had a positive impact on their rotation. 38/43 residents (88%) believed the debriefing reduced sentiments of cynicism and dissatisfaction caused by emotional distress related to EOL care. Conclusions: Resident concerns about death decreased during a 4-week inpatient oncology rotation in which a structured debriefing program occurred during week 3. Although the study protocol does not provide causation, it suggests the debriefing allowed residents to reflect on EOL care and enhance their ability to cope with distress. The favorable feedback from this pilot led to a permanent curricular change for the inpatient oncology rotation. Strategies to assess and manage emotional strain among residents providing EOL care remain limited and warrant further investigation.[Table: see text]