bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between global longitudinal strain (GLS), N-terminal-prohormone brain natriuretic peptide (NT-proBNP) and subsequent cardiomyopathy (CM) in a clinically assessed cohort of childhood cancer survivors exposed to cardiotoxic therapy.
Authors: Ehrhardt Matthew J. , Liu Qi , Jefferies John L. , Mulrooney Daniel A. , Sapkota Yadav , Goldberg Jason , Dixon Stephanie B , Lucas John Thomas , Ness Kirsten K. , Srivastava Deo Kumar , Mazur Wojciech , Plana Gomez Juan Carlos , Robison Leslie L. , Yasui Yutaka , Hudson Melissa M. , Armstrong Gregory T. 
Published: June 2022

10052 Background: Among survivors exposed to anthracycline or chest radiation (RT) who have an ejection fraction (EF) of ≥50%, the utility of GLS and NT-proBNP to identify survivors who are at highest risk for future CM is unknown. Methods: Survivors participating in the St. Jude Lifetime Cohort, ≥5 years from cancer diagnosis and at risk for CM per the International Guideline Harmonization Group (IGHG), underwent baseline surveillance echocardiography. A baseline GLS and NT-proBNP was also performed for survivors with an EF ≥50%. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of CM (graded per modified Common Terminology Criteria for Adverse Events v4.0) based on abnormal baseline GLS (≥ -18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles) adjusted for age at baseline assessment, age at diagnosis, sex, race, hypertension, diabetes, obesity, and IGHG risk group (Table footnote). Results: Among 1598 at-risk survivors (median age 35.1, range 9.4-68.8 years), all had GLS and 1110 NT-proBNP at baseline. 165 (10.3%) developed CM ≥ grade 2 at a median follow-up of 5.2 (0.7-10.0) years. IGHG moderate- and high-risk survivors exposed to anthracyclines were at increased risk of CM at follow-up if both baseline GLS and NT-proBNP were abnormal (HR=3.4, 95% CI: 1.9-5.8; Table) or GLS was abnormal and NT-proBNP not assessed (HR=3.8, 95% CI: 2.0-7.2), or when GLS was normal and NT-proBNP was abnormal (HR=1.9, 95% CI: 1.1-3.4). Abnormal GLS and/or NT-proBNP were not associated with increased risk of CM in IGHG low-risk survivors or in those defined as moderate- to high-risk due to chest RT only. Conclusions: Among long-term survivors of childhood cancer exposed to >100 mg/m2 anthracycline, abnormal GLS and NT-proBNP identified those survivors at increased risk of future CM despite an EF ≥50% on surveillance echocardiography. Conditional surveillance strategies utilizing GLS and NT-proBNP may benefit moderate- to high-risk survivors. [Table: see text]
Prevalence of incidental pathogenic germline variants detected in cfDNA in patients with oncogene-driven non-small cell lung cancer.
Authors: Mezquita Laura , Bucheit Leslie A. , Laguna Juan Carlos , Pastor Belen , Teixido Cristina , Gorria Teresa , Albarran-Artahona Victor , Garcia de Herreros Marta , Reyes Roxana , Reguart Noemi , Vinolas Nuria , Arcocha Ainara , Puig-Butillé Joan Anton , Drusbosky Leylah , Faull Iris , Castro Elena , Patel Jyoti D. , Prat Aleix , Besse Benjamin 
Published: June 2022

10569 Background: Preliminary data has highlighted inherited predisposition to lung cancer (LC) related to certain pathogenic germline variant (PGV) in cancer predisposing genes, including patients (pts) with tumors harboring somatic driver oncogene alterations (alt); however, the frequency of PGV in LC is unknown. Liquid biopsy assays may be able to identify incidental PGV (iPGV) in pts with solid tumors at scale. Here, we report the prevalence of iPGV in genes predisposing to cancer in pts with advanced non-small cell LC (aNSCLC) relative to driver alt status. Methods: Genomic results were retrospectively queried from 31126 pts with aNSCLC who had Guardant360 testing as part of routine clinical care from 10/2020-12/2021. iPGVs were defined as being non-synonymous, non-VUS alt in selected genes known to increase lifetime cancer risk (Table) with variant allele frequency (VAF) >30% and pathogenicity defined by a proprietary bioinformatics pipeline. Clinical factors such as age, gender, histology, and diagnosis status (new/progressing) were extracted from test requisition forms. The driver group included guideline-recommended and emerging somatic mutations (m) in EGFR/KRAS/BRAF/MET/HER2, fusions (f) in ALK/ROS1/RET/NTRK1-3 and amplifications (a) in HER2/MET. Results: Out of 31126, 720 (2.3%) of pts had predicted iPGV, of whom 54% were female, with a median age of 64 (22-100); most pts were newly diagnosed (66%). Among them, 92% of pts had iPGVs identified in the homologous recombination and repair (HRR) pathway, 3% in mismatch repair (MMR) pathway and 5% EGFR iPGVs. A total of 335 (47%) pts with iPGVs had somatic driver alt (Table): 20% of pts with iPGV had KRASm (n=144/720; 67 G12C), 12% EGFRm (n=87; 28 ex19del, 35 ex21(L858R)), 2.5% BRAFm (n=18), 2.5% METm ex14 skip (n=18), 0.1% HER2m (n=1), 0.8% ALKf (n=6), 0.1% ROS1f (n=1), 0.1% RETf (n=1), 0.1% HER2a (n=1), and 0.4% METa (n=3). ATM iPGVs were enriched in pts with driver alt. (45% driver vs 27% non-driver, p<0.0001) while BRCA1 iPGVs were more frequently observed in pts without driver alt. (17% vs 8%, p<0.0001). Distribution of other iPGVs was similar across driver/non-driver groups. Conclusions: In this large cohort, 2.3% of pts with aNSCLC were iPGV-carriers; 47% of pts had oncogene-driven tumors, particularly with KRAS, EGFR, BRAF and MET alt. iPGV and lung carcinogenesis need further evaluation to define the role of genetic predisposition in LC risk and to determine the highest risk individuals to explore screening and therapeutic strategies, such as in pts with other solid tumors. [Table: see text]
Co-occurrence of germline pathogenic variants in Chinese patients with solid tumors.
Authors: Zhang Yan , Han Tiantian , Guo Didi , Luo Ningning , Lu Guanghua , Bu Fanfeng 
Published: June 2022

10579 Background: Germline mutations play an important role in cancer risk and susceptibility. With the growing implementation of next generation sequence of multiple gene panel, an increasing number of cases that carry two or more inherited cancer-predisposing alleles in the same individual are being described. However, understanding the impact of these combined mutations on the patient's phenotype can be particularly challenging. To further understand these combined mutations, we analyze the genetic susceptibility mutations of Chinese solid tumor patients to explore the characteristics of multiple germline variants. Methods: Genetic mutations were reviewed in cancer patients who underwent hybridization capture based next-generation sequencing (NGS). The pathogenicity of germline mutations was categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines, and only pathogenic and likely pathogenic variants were included in this study. Results: Germline variants were identified in 1267 individuals, including 1244 patients harbored one germline mutations and 23 patients carried ≥2 germline mutations, and there was no age difference in the two groups (57 vs 55, p = 0.62). In the ≥2 germline mutations group, genes most frequently involved were BRCA1/2 (12/47, 25.5%), CHEK2 (4/47, 5,1%), TP53(4/47, 5,1%) and MUTYH (4/47, 5,1%). Most of these variants affected DNA damage repair pathways [57% homologous recombination repair (HR), 15% mismatch repair (MMR)]. Besides, double variants in HR and HR pathway were found in 8 patients, HR and MMR pathway were found in 5 patients. Surprisingly, the 50-year-old man with colorectal cancer with three pathogenic variants of the [ FH - BRCA2- FANCD2] genes showed a high aggregation of tumors associated with leiomyomatosis and renal cell cancer and HBOC. Conclusions: We found over 56.5% patients with multiple pathogenic variants in DNA damage repair pathways, which may have important implications for the treatment strategy for these patients. Next-generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes, which could guide the clinician as to what the effect of each combination of mutations might be.
Implementation of universal, pan-cancer germline genetic testing in patients with cancer in Jordan.
Authors: Abdel-Razeq Hikmat , Tbakhi Abdelghani , Abuhijlih Ramiz , Abujamous Lama , Al Masri Mahmoud , Abukhashabeh Razan , Mitchell Asia , Heald Brandie , Nielsen Sarah M. , Nussbaum Robert Luke , Esplin Edward D. 
Published: June 2022

10580 Background: Detection of pathogenic germline variants (PGVs) has a significant and growing impact on the management of patients with many types of cancer. Most research to date evaluated individuals of European background, which can result in skewed genetic testing criteria and variant interpretation. Additional data are needed from diverse populations. This study aimed to investigate a universal germline testing strategy and the pattern and frequency of PGVs among all newly diagnosed cancer patients at a single center in Jordan. Methods: In this prospective, observational study, consecutive patients newly diagnosed with cancer were classified as meeting or not meeting National Comprehensive Cancer Network (NCCN) germline genetic testing criteria. All patients underwent an 84-gene panel test, independent of age, stage or family history. Demographics and clinical history were collected and analyzed from information provided by the clinicians on the test requisition form. Descriptive statistics were employed, and statistical significance was determined by two-tailed Fisher’s exact test and unpaired t test. Results: In total, 1377 cancer patients of Arabic background were enrolled, of which 831 (60.3%) met NCCN criteria (Table). PGVs were identified in 210 (15.3%). Excluding the 29 patients who were carriers for autosomal recessive conditions, 192 PGVs were identified in 181 (13.1%) patients. PGVs were most commonly identified in APC (p.I1307K variant, 55, 28.6%), BRCA2 (35, 18.2%), BRCA1 (21, 10.9%), and TP53 (12, 6.3%). While patients who met NCCN testing criteria were more likely to have a PGV (p<0.0001), 44 (24.30%) patients with PGVs did not meet criteria. Among those with PGVs, 177 (97.8%) were potentially eligible for increased screening per NCCN/expert opinion guidelines, 69 (38.1%) targeted therapies, and 89 (49.2%) clinical trials; this included 41 (22.7%), 6 (3.3%), and 14 (7.7%) patients, respectively, that did not meet NCCN testing criteria. 1445 variants of uncertain significance (VUS) were identified in 833 (57.7%) patients, but no difference in VUS rate was observed between those meeting and not meeting criteria (p=0.7354). Conclusions: Overall PGV rate among cancer patients from one center in Jordan was similar to that reported in the literature. While the VUS rate was high, similar rates were observed in those meeting and not meeting criteria. Testing restricted to guidelines could have missed approximately a quarter of patients with PGVs, >95% of whom might qualify for increased screening, targeted therapies, and/or clinical trials. [Table: see text]
Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR+/HER2- advanced breast cancer: A phase Ib study.
Authors: Zhang Qingyuan , Zhang Pin , Yan Min , Yan Xi , Wang Xian , Gu Yuanting , Qu Xiujuan , Li Shaorong , Xu Guoying , Yang Wenhui , Zhu Xiaoyu , Zhang Xiaojing , Xu Binghe 
Published: June 2022

1066 Background: Dalpiciclib (Dalp; SHR6390) is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary clinical activity as monotherapy for pretreated advanced breast cancer (ABC). Here we conducted a multicenter, phase 1b trial to further assess the safety, pharmacokinetics and efficacy of Dalp in combination with endocrine therapy (ET) in HR+/HER2- ABC. Methods: 5 cohorts of patients with HR+/HER2- locally recurrent or metastatic BC and any menopausal status were enrolled (~15 patients/combination regimen). Patients without prior treatment for ABC (cohort1/2) were given Dalp (125 or 150 mg po qd, d1-21, q4w) plus letrozole (LTZ; 2.5 mg po qd) or anastrozole (ATZ; 1 mg po qd); patients who progressed after ET (cohort 3-5) were given Dalp (125, 150, or 175 mg po qd, d1-21, q4w) plus fulvestrant (Fulv; 500 mg im, cycle 1 d1, d15, then d1 q4w). The primary endpoint was safety. The data cutoff date was Sep. 20, 2021. Results: 58 patients received Dalp plus LTZ/ATZ and 46 received Dalp plus Fulv. No maximum tolerated dose of Dalp was reached with LTZ/ATZ or Fulv. Across all cohorts, 75.0%-93.8% of patients had a grade ≥3 treatment-related adverse event (TRAE), with the most common being neutropenia (grade 3, 40.0%-87.5%; grade 4, 4.2%-46.7%) and leukopenia (grade 3, 33.3%-80.0%; grade 4, 0%; Table). Treatment-related serious AEs occurred in 2 (3.4%) patients with Dalp plus LTZ/ATZ and none with Dalp plus Fulv. At the tested dose levels, steady-state areas under the concentration curve and peak concentration of Dalp increased with dose in combination with LTZ/ATZ or Fulv. Dalp 150 mg was associated with a numerically higher objective response rate in both ET-untreated (67.6%, 95% CI 49.5-82.6) and ET-pretreated (53.3%, 95% CI 26.6-78.7) patients per investigator. The median progression-free survival with Dalp 150 mg was 20.3 mo (95% CI 16.9-not reached [NR]) and 16.7 mo (95% CI 1.9-24.1) in ET-untreated and ET-pretreated patients respectively. Conclusions: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile, with hematological toxicities as the most common TRAEs. The recommended phase 3 dose of dalpiciclib was 150 mg. Together with the promising anti-tumor activity observed with the combination therapy in HR+/HER2- ABC, further trials are warranted. Clinical trial information: NCT03481998. [Table: see text]
Effect of transition from inpatient oncology service to oncology consult service on fellow burn out and training.
Authors: Tariq Anosha , Aijaz Talha , Katiyar Vatsala , Rojan Adam 
Published: June 2022

11023 Background: The hematology-oncology inpatient service at the University of Louisville underwent a major change in July 2021 from a medical oncology service run by hematology/oncology fellows and attendings to a hospitalist-run service with hematology/oncology fellows and attendings sharing patient care responsibility as a consulting service. We planned this study because, to date, no published work has studied the effect of transitioning from an inpatient to consult service on fellow burnout, education, and training. Methods: A survey was distributed in July 2021, and a follow-up survey was sent in January 2022. The survey had 38 questions regarding the impact of the workload on time for study, research, personal and professional life, which were scored from 1 to 5. Two tail paired t-test was used to compare the difference in means. The survey also contained questions from the Mayo Clinic Resident Well-Being Index (RSWBI). This index has been validated to identify distress among fellows and allows for the comparison of local results with national data from RSWBI. In RSWBI, scores range from 0-7, with 0 being the lowest risk and 7 being the highest risk of burnout. A cut-off of a score ≥ 5 identifies individuals with a high degree of distress, is associated with an increased risk of error, suicidal ideation, and burnout, and has been validated in more than 1700 residents/fellows. Results: We distributed the survey to 2nd and 3rd-year fellows. 5/6 fellows completed the survey. 3 of them were male and 2 females. Change in inpatient service structure did not impact time for study, research, patient encounter, or ability to handle the volume of work. Improvement in adequate time preparing for clinic was statistically significant (P=0.03), and other improvements were also noted in concentration, time for family, and better personal and professional relationships (Table). RSWBI median score before the transition was 3.6, which improved to 2.0 after the transition to consulting service, which was similar to the national average where the median score was 2.0 among 8237 residents/fellows. 2 fellows (40%) were at high risk of distress before the transition. 1 fellow (20%) was at high risk of distress after the transition, which was comparable to the national average where 19.4% resident/fellows scored ≥5. Conclusions: These results show increased levels of distress in fellows that improved to the national average following transition from a primary inpatient medical oncology service to a consult service.[Table: see text]
The need to develop the career pathway in oncology as an opportunity to improve the satisfaction of young oncologists in Spain: A national survey by the Spanish Society of Medical Oncology (SEOM) + mir section.
Authors: Jiménez Labaig Pablo , Sánchez Domingo Antonio , Sesma Andrea , Quilez Alicia , Pacheco Barcia Vilma , Obispo Berta , Paez David , Quintanar Maria Teresa , Sánchez-Cánovas Manuel , Tarazona Noelia , Fernandez Montes Ana , Felip Enriqueta , Rodriguez-Lescure Alvaro , Elez Elena 
Published: June 2022

11038 Background: A long-term planning of the oncologists’ career path is essential to approach the continuous changes in the oncology field given the need of further subspecialization after the training period. Our aim is to evaluate the current professional development of young medical oncologists in Spain and seek improvement strategies to enhance their careers in order to guarantee commitment with research and improve in patient care and outcomes. Methods: The SEOM +MIR Section launched a national online survey in May 2021 aimed at young medical oncology consultants (<6 years of experience) and last year medical oncology residents. Spanish professionals were invited to participate via email through the SEOM database. A descriptive analysis was performed using R software v4.1.2. Results: A total of 162 responses were eligible. 103 (64%) were women. 129 (80%) were consultants and 33 (20%) were residents. 92 (68%) performed standard clinical care and 11 (7%) research activity. 118 (73%) were subspecialized in a main area of interest and almost half of them, 70 (59%), chose it because it was the only option available after finishing residency. 87 (54%) had considered different employment opportunities other than standard clinical care and 38 (23%) showed an interest in enhancing their research activity. 141 (87%) showed relevant concern about their employment stability (table attached). 82 (51%) had considered working abroad: 33 (44%) outside European Union. The main reasons were: 132 (81%) believed the professional standing in Spain was worse than other countries, 41 (25%) thought it might increase their professional development and 33 (20%) argued for better salary conditions abroad. Among them, 21 (13%) had signed at least 4 contracts and 66 (41%) had ≥5 employment contracts in the last 5 years. 27% of respondents indicated that the figure of the boss had been the most contributing professional in their professional career. The mentor (20%) and the tutor (18%) also stand out as relevant figures in terms of professional development. Up to 27% of the sample refers not to have obtained any help from the figures mentioned. Conclusions: An absence of engagement in the long-term career paths of young medical oncologists in Spain was observed. Research is not defined in the current early professional life. Furthermore, there is a lack of contractual quality and planning for the entry into the labour market of newly trained oncologists. The lack of such a career pathway has consequences that encourage the search for employment opportunities different from clinical care and in other countries. [Table: see text]
A novel oral paclitaxel and HM10381 (oraxel)-treated metastatic breast cancer: A phase I study (KX-ORAX-CN-007).
Authors: Qin Tao , Lai Xiuping , Wang Ying , Wang Jing , Chen Junyi , Zhang Yiwen , Wu Junyan , Song Erwei , Yao Herui 
Published: June 2022

1104 Background: This phase I study assessed the pharmacokinetics, safety, antitumor activity of oral paclitaxel and HM10381 (Oraxel) in patients with metastatic breast cancer. Methods: Oraxol (oral paclitaxel 205 mg/m2 plus HM30181A 15 mg) daily for 3 consecutive days weekly for up to 16 weeks was administered to patients. The primary objective endpoint was pharmacokinetic analysis. The secondary endpoint were objective response rate (ORR) and safety. For pharmacokinetic analysis, timed blood samples were collected. Results: Twenty-four female patients were enrolled from Apr 2019 to Aug 2019. The median age was 53 years (range: 35 to 70 years). The mean lines and median line of treatment were 2.5 and 2, respectively. Previous breast cancer treatments included chemotherapy in 23 (96%) patients, hormonal therapy in 20 (83%) patients. Prior taxanes therapy was reported in 20 (83%) patients. There were 15 patients in efficacy dataset. The best ORR (Investigator) was PR in 40%, SD in 53%, and PD in 7%. The best overall response rate (ICRRC) was PR in 36%, SD in 57%, and PD in 7% of patients. There were no hypersensitivity-type reactions. Adverse events of interest neutropenia, neurotoxicity, and diarrhea were reported as 20 (83%)，7 (29%) and 11 (46%), retrospectively. A total of 15 (63%) patients experienced Grade ≥3 TEAEs, including neutrophil count decreased in 11 (46%) patients, WBC count decreased in 8 (33%) patients. Treatment related SAE was reported in 1 (4.17%) patient experienced febrile neutropenia, pneumonia, and septic shock. The PK data indicated that the efficacy response is not associated with oral paclitaxel exposure parameters AUC or Cmax. Conclusions: The study showed that Oraxol as novel oral chemotherapy agent shows promising antitumor activity in patients with metastatic breast cancer, manageable toxicity, and no hypersensitivity-type reactions. Clinical trial information: NCT04993040.