bluuebunny/crossref_metadata_2025_split huggingface dataset:
On-treatment derived neutrophil-to-lymphocyte ratio and response to palbociclib and letrozole: Analysis of a multicenter retrospective cohort and the PALOMA-2 study.
Authors: Kim Chang Gon , Kim Min Hwan , Kim Jee Hung , Kim Seul-Gi , Kim Gun Min , Kim Tae Yeong , Ryu Won-Ji , Kim Jeeye , Park Hyung Seok , Park Seho , Cho Youngup , Park Byeong-Woo , Kim Seung Il , Jeong Joon , Sohn Joohyuk 
Published: June 2021

1066 Background: Relevant predictive biomarkers for cyclin dependent kinase 4 and 6 (CDK4/6) inhibitors have not been identified in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). We investigated whether dynamic changes in the peripheral immune cells can predict therapeutic response to CDK4/6 inhibitors in ABC with translational relevance. Methods: Postmenopausal women who received palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (n = 221; exploratory cohort). Pre- and on-treatment leucocyte, neutrophil, lymphocytes counts, neutrophil-to-lymphocyte ratio (NLR), and derived NLR (dNLR; neutrophil/[leucocyte-neutrophil]) were correlated with survival outcomes. Patients from the PALOMA-2 study (NCT01740427) treated with letrozole with or without palbociclib (n = 410 and 209, respectively) were analyzed for validation (validation cohort). Prospectively enrolled patients were subjected to immunophenotyping with flow cytometry to explore the immune cell dynamics after CDK4/6 inhibitor treatment. Results: In the exploratory cohort, palbociclib administration significantly reduced leucocyte, neutrophil, and lymphocyte counts on cycle 2 day 1. Not baseline, but on-treatment neutrophil and lymphocyte counts were associated with superior and inferior outcomes, providing predictive significance to on-treatment NLR and dNLR for progression-free survival (PFS; HR = 1.64 and 2.52; all P< 0.001). In the validation cohort, higher on-treatment dNLR was associated with inferior PFS in patients treated with palbociclib and letrozole (HR = 1.50 and P= 0.009 with 1.04 cut-off), whereas not correlated with outcome in placebo and letrozole-administered patients. Exploratory analysis revealed that CDK4/6 inhibitor prevented T cell exhaustion and diminished relative frequencies of myeloid-derived suppressor cells, both of which trigger antitumor immunity. Conclusions: On-treatment dNLR significantly predicted treatment outcome in HR-positive, HER2-negative ABC treated with palbociclib and letrozole, allowing early prediction of treatment response with mechanistic insights. Clinical trial information: NCT01740427 .
Apatinib plus vinorelbine versus vinorelbine for advanced triple-negative breast cancer with failed first or second-line treatment: The NAN trial.
Authors: Li Doudou , Tao Zhonghua , Wang Biyun , Wang Leiping , Cao Jun , Hu Xichun , Zhang Jian 
Published: June 2021

1075 Background: No standard treatment exists for triple negative breast cancer (TNBC) with failure of multi-line therapies. Apatinib is a small-molecule tyrosine kinase inhibitor that has promising anti-angiogenesis and antitumor activity for TNBC. We aimed to evaluate the safety and efficacy of adding apatinib to chemotherapy in patients with metastatic TNBC with failed first/second-line treatment. Methods: This randomized, open-label, phase 2 trial recruited patients with advanced TNBC who failed to receive first or second-line treatment. A total of 66 patients were randomly assigned, in a 1:1 ratio, to receive vinorelbine 25 mg/m2 (days 1, 8, 15) or vinorelbine 20 mg/m2 (days 7, 14, 21) with apatinib (250 mg once daily, days 1-5, 8-12, 15-19, if tolerable, the second cycle started with 500 mg per day) in 28-day cycles. The efficacy was evaluated every two treatment cycles (8 weeks ± 3 days). According to the RECIST criterion, patients with CR, PR and SD continued treatment until disease progression or unacceptable toxicity or withdrawal of consent. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rate (ORR) and safety. Results: Between Sep 14, 2017 and Dec 08, 2020, 66 patients underwent randomization. Median follow-up was 21.3 months. 33 received apatinib plus vinorelbine and 32 received vinorelbine (1 was withdrawal of consent). Median PFS was significantly longer in the apatinib plus vinorelbine group than in the vinorelbine group (3.8 months vs. 1.9 months; hazard ratio for disease progression or death, 1.76; 95% confidence interval [CI], 1.02 to 3.05; P= 0.039). Median OS was 14.6 months with apatinib plus vinorelbine and 14.1 months with vinorelbine (HR,1.34; 95% CI, 0.60 to 3.00; P= 0.469). The ORR was 48.5% in the apatinib plus vinorelbine group and 31.3% in the vinorelbine group ( P= 0.156). The most common treatment-related hematologic grade 3–4 adverse events in those treated with apatinib plus vinorelbine versus vinorelbine, respectively, were leukopenia (42.4% vs. 34.4%), granulocytopenia (57.6% vs. 28.1%), anemia (9.1% vs. 12.5%) and thrombocytopenia (3.1% vs. 3.0%). The most frequent grade 3 nonhematologic toxicities were hand–foot syndrome (21%), proteinuria (9%), hypertension (9%) and increased ALT (9%) and which only occurred in apatinib plus vinorelbine group. No treatment-related nonhematologic grade 4 adverse events or treatment-related deaths were observed. Conclusions: Collectively, among patients with advanced TNBC with failed first/second-line treatment, apatinib plus vinorelbine show a promising benefit in PFS compared to vinorelbine monotherapy. Apatinib plus vinorelbine regimen shows promising efficacy and manageable toxicity, which might be a previously unappreciated therapeutic option for advanced TNBC. Clinical trial information: NCT03254654 .
A phase II trial of stereotactic radiation therapy and in situ oncolytic virus therapy in metastatic triple-negative breast cancer (mTNBC) patients followed by pembrolizumab (STOMP).
Authors: Sun Kai , Ensor Joe E. , Xu Yitian , Zhang Licheng , Guerrero Carlo , Niravath Polly Ann , Patel Tejal Amar , Geyer Charles E. , Jain Dharamvir , Teh Bin S. , Farach Andrew M. , Sultenfuss Mark , Gupta Nakul , Schwartz Mary R. , Haley Susan , Mejia Jamie , Butler E. Brian , Bernicker Eric , Chen Shu-Hsia , Chang Jenny Chee Ning 
Published: June 2021

1079 Background: Pembrolizumab, stereotactic body radiotherapy (SBRT), and viral vector-based gene therapy such as adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus ganciclovir have each shown antitumor immune activity. The combination of those modalities may represent a window of opportunity to enhance pembrolizumab efficacy in mTNBC patients. Methods: In this single-arm, open-label phase II trial, mTNBC patients were treated with in situ oncolytic ADV/HSV-tk (5 x 1011 vp) intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab until progression or intolerable toxicity. Response was assessed in non-irradiated metastatic sites. The primary end point was clinical benefit rate (CR, PR and SD per RECIST version1.1). Secondary endpoints included duration on treatment (DoT) and safety. Immune correlative analysis with peripheral blood CYTOF (D1 baseline, D7 and D38), and tissue imaging mass cytometry (IMC) with 35 cell surface markers was performed on paired biopsies (D1 baseline and D17). Results: 28 mTNBC patients were enrolled; 18 (64.3%) had PD-L1 negative tumors. Median age was 54 years (range 34-78). Median prior lines of chemotherapy were 2 (range 0-6), with 8 (28.6%) having received >3. 3 (10.7%) had brain metastases. Clinical benefit was seen in 6 (21.43%) patients; 2 CR (7.1%),1 PR (3.57%) and 3 SD (10.7%). Patients who had clinical benefits had durable responses, with median DoT of 383 days (range 195-1195). One patient who had CR, but discontinued pembrolizumab due to Grade 3 pneumonitis, has remained disease free without any systemic therapy for 39 months. The combination was well tolerated; 9 (32.1%) patients had Grade 3- 4 AEs. Pre- and post-therapy CYTOF analysis showed significant association between immune biomarkers with clinical responses (AUC 0.75, Cohen’s Kappa 0.364). Tumor PDL1 was independently associated with response (AUC 0.70, Cohen’s Kappa 0.347); AUC for PDL1 together with immune biomarkers is 0.85. Conclusions: ADV/HSV-tk gene therapy followed by radiation therapy and then pembrolizumab is a well-tolerated promising treatment in heavily pretreated mTNBC patients. Early detection of increased effector and effector memory CD8 T cells and nonclassical monocytes correlates with response and non-response respectively. Clinical trial information: NCT03295916 .[Table: see text]
Survival time in urban center breast cancer patients with CNS metastasis with or without visceral metastasis.
Authors: Klahr Miriam Pearl , Deng Junwen , Anampa Mesias Jesus Del Santo 
Published: June 2021

1088 Background: There is limited data about the role of isolated central nervous system (CNS) metastasis (mets) in patients with breast cancer (BC), since prior studies evaluated BC patients with CNS plus visceral mets. Furthermore, though Black race is associated with worse BC outcomes, there are few studies on CNS mets that predominantly included racial and ethnic minorities in their cohorts. Our study compares overall survival (OS) in BC patients with CNS involvement with and without visceral mets in an underrepresented patient population. Methods: This is a retrospective case series study. We used Montefiore’s Clinical Looking Glass software to identify patients. Inclusion criteria were females age ≥18 years at our institution with the diagnosis of BC and CNS mets between 3/31/1997 to 3/31/2019. Chart review was conducted to obtain clinical-pathological features, including date of diagnosis, treatment, clinical course, and survival status. Patients with BC and CNS mets were divided into two cohorts, those with additional mets limited to bone and lymph nodes but without further visceral spread (CNS-NV), and those with CNS mets plus visceral mets (CNS-V). Kaplan-Meier methods were used to analyze the median OS. Results: Our study included a high proportion of underrepresented minorities (n=177); 46.3% were Black, 10.7% were White, and 34.5% were Other Race; besides, 28% were Hispanic. Mean age at diagnosis of CNS mets was 58 years (SD = 12.9). 62.1% were estrogen receptor (ER) and/or progesterone receptor (PR) positive, 27.1% were HER2 positive; and 19.8% were ER, PR and HER2 negative. Mean number of chemotherapy and endocrine therapy lines before CNS mets were 2 (IQR = 1-2) and 1 (IQR = 1-2), respectively. CNS-NV and CNS-V cohorts included 35 and 142 patients, respectively. Patients with CNS-NV had longer OS than CNS-V (2118 vs. 1120 days, p=0.02). Further subgroup analysis for group CNS-NV was performed based on treatment modality. In this cohort, OS was not significantly different between patients who did and did not receive chemotherapy (n =35, mean OS 1509 vs. 960 days, p = 0.49). In addition, OS was not significantly different between patients who received and did not receive endocrine therapy (n = 24, mean OS 857 vs. 1394 days, p = 0.4). Finally, OS did not significantly differ between patients who did and did not receive anti HER2 treatment (n = 11, 1753 vs. 849 days, p = 0.15). Conclusions: Minimal research has been conducted on breast cancer patients with CNS mets and distal involvement limited to the bones or lymph nodes. In a heterogenous racial and ethnic population, patients with BC and CNS mets have prolonged OS if the extent of distal involvement is limited to the bones or lymph nodes, compared to those with visceral mets. More research with larger sample sizes is needed to confirm our findings, which may help to de-escalate and tailor treatment for patients with CNS mets.
Sexual harassment of oncologists.
Authors: Subbiah Ishwaria Mohan , Markham Merry Jennifer , Graff Stephanie L. , Matt-Amaral Laurie Beth , Close Julia Lee , Griffith Kent A. , Jagsi Reshma 
Published: June 2021

11001 Background: Few studies have used comprehensive validated measures to investigate the incidence and impact of workplace sexual harassment experienced by physicians (and none, to our knowledge, by oncologists). Methods: We conducted a cross-sectional survey of ASCO’s Research Survey Pool with targeted social media outreach to examine the prevalence and types of sexual harassment (SH) experienced by oncologists. Using the Sexual Experiences Questionnaire (SEQ), we measured their work experience of three SH forms (gender harassment [GH], unwanted sexual attention [USA], sexual coercion [SC]) in the past year by institutional insiders (peers/superiors) and patients/families separately. Controlling for race, career stage & specialty, multivariable (MV) regression models assess the impact of SH (independent variable) on 4 dependent variables of mental health (MHI5), perceptions of workplace safety (single item), job satisfaction (MOAQ) & 3-item measure of turnover intentions (in non-trainees). Results: Of 271 respondents, 250 were physicians in practice and 21 were residents/fellows; 153 (56%] were women, 168 (62%) practiced in academic settings & 227 (84%) were medical oncologists. SH by peers/superiors was reported by 189 (70%) overall, including 80% of women and 56% of men (p<0.0001). GH was reported by 79% of women and 55% of men (p<0.0001), USA by 22% of women and 9% of men (p=0.005), and SC by 3% of women and 2% of men (p=0.42). SH by patients and/or families was reported by 67% of women and 35% of men (p<0.0001), GH by 66% of women and 34% of men (p<0.0001), USA by 5% women and 6% men (p=0.80), and SC by 1% women and 1% men (p=0.72). MV analysis showed past-year SH from peers/superiors was significantly associated with decreased mental health (β -0.45, p 0.004), workplace safety (β -0.98, p<0.001) and increased turnover intentions (β 0.93, P<0.0001). SH from patients/families was similarly significantly associated with mental health (β -0.41, p 0.002), workplace safety (β -0.42, p 0.014) and turnover intentions (β 0.58, p 0.0004). SH from insiders (β -0.64, p 0.001) but not patients (p 0.55) was significantly associated with job satisfaction. Furthermore, there were no significant interactions between the respondents’ gender and the SH scores in any of the models of impact. Conclusions: This is the first study in oncology to systematically characterize the incidence of sexual harassment experienced by oncologists. Our findings demonstrate the impact of sexual harassment on men and women oncologists on multiple domains of workplace experience. This study provides critical data to inform the need for and design of effective protective and preventive workplace policies in oncology.
Gender and racial/ethnic disparities in academic oncology leadership.
Authors: Jones Gavin , Dhawan Natasha , Chowdhary Akansha , Royce Trevor Joseph , Patel Kirtesh R. , Chhabra Arpit , Knoll Miriam , Deville Curtiland , Winkfield Karen Marie , Vapiwala Neha , Duma Narjust , Chowdhary Mudit 
Published: June 2021

11009 Background: Gender & racial/ethnic leadership disparities have been independently identified in academic hematology/oncology (HO) and radiation oncology (RO). Here, we evaluate gender and racial/ethnic intersectionality from the trainee to the leadership level. Methods: All ACGME accredited HO and RO training program websites were queried to identify constituent trainees, academic faculty, program directors (PD) and department chairs (DC), with a leadership position defined as PD or DC. Individual gender & race/ethnicity was determined using externally validated software tools (Gender-API, NamSor, & Onolytics), publicly available descriptors, and image review. We grouped individuals into 6 categories: White Male (WM), White Female (WF), Asian Male (AM), Asian Female (AF), Underrepresented Groups in Medicine (as defined by AAMC) Male (URMM) and Female (URMF). The chi-squared goodness-of-fit test was applied to examine if deviations exist between the observed vs. expected proportions of gender/race dyads in trainees, PD, and DC compared to academic faculty. Results: We identified 7,722 individuals from 2019-2020: 1,759 trainees (HO=1525; RO=234), 5,726 faculty (HO=4834; RO=892), 242 PD (HO=149; RO=93) and 237 DC (HO=144; RO=93). Leadership positions were most often comprised by WM (52.6%), and least often comprised by URMF (2.9%). Combined HO/RO analysis revealed significant differences in the observed representation of trainees & DC vs expected levels based on total faculty, respectively: WM (33.7% & 60.3% vs. 42.3%), WF (19.2% & 13.9% vs. 22.3%), AM (20.75% & 16.9% vs. 16.4%), AF (17.9% & 2.5% vs. 12.7%), URMM (4.09% & 5.5% vs. 3.5%) and URMF (4.3% & 0.8% vs. 2.8%), p<0.01. No differences were seen between PD vs total faculty. On subset analysis, there were significant differences observed in HO programs at the trainee, PD and DC levels compared to total faculty, whereas significant differences in RO programs were seen only at the DC level [Table]. Conclusions: Gender & racial/ethnic disparity is present in academic oncology. Specifically, women of all races/ethnicities are proportionally underrepresented in DC positions in HO and RO programs. These data can serve as a benchmark to raise awareness and monitor progress towards a more balanced workforce in oncology.[Table: see text]
The clinician educator career in oncology.
Authors: Giuliani Meredith Elana , Bhadkamkar Nishin , Lubner Sam Joseph , Tibbits Michal , Tseng Jennifer , Von Roenn Jamie H. 
Published: June 2021

11022 Background: There has been progress in both the definition of the work of a clinician educator (CE) and the skillset required. The CE career pathway has not been studied in oncology. Our aim is to study the current state of oncologists’ identification as a CE and their perceptions of the barriers and enablers for a CE career. Methods: A 27-item cross-sectional survey was completed by ASCO program directors (PDs) and associate/assistant PDs (APDs). The survey asked about their current career and perceptions about CE careers including barriers/enablers. Prior to distribution, the survey was reviewed by experts in oncology education and approved by the ASCO Education Council. Frequency statistics are presented. Results: Eighty-eight of 297 PDs/APDs responded (30%). 70 (80%) perceived CE as a viable career track, 48 (55%) had a CE track available to faculty at their institution and 72 (82%) considered themselves as a CE. Most PDs/APDs (59; 67%) reported no formal medical education training for their trainees and the majority (67; 76%) did not have a CE track for their fellows. While medical education responsibilities are perceived to be common amongst graduates (39% reporting >50% of graduates), 59 (67%) of PDs/APDs reported <10% of their trainees pursue medical education as a research focus. Compared to clinical, laboratory or discovery research, 71 (81%) of PDs/APDs felt their fellows were less or significantly less prepared for a career in education research. Table highlights the perceived barriers/enablers to a CE career. Conclusions: Many PDs/APDs perceive themselves as clinician educators. However, little to no formal education training currently exists to identify and nurture trainees into careers in education. Identification of training milestones in education and establishing guidelines for academic promotion for CEs in oncology are needed.[Table: see text]
Impact of advanced clinical and translational research educational programs on oncology specialties and career development.
Authors: Simkins Aron , Lee Michael , Paez Wencesley A. , Arana Yi Cecilia , Kosiorek Heidi E. , Curtis Michael , Mitin Timur 
Published: June 2021

11026 Background: The Clinical and Translational Science Award (CTSA) Program currently supports more than 50 leading medical research institutions in the U.S. with the aims of training, promoting and developing future translational science researchers, with particular emphasis on advanced Clinical and Translational Research (CTR) education. No prior studies have evaluated career development in oncologists who have completed CTR training. The objective of this study is to examine the impact of advanced CTR training on career development, return-on-investment and research productivity in Oncology specialties. Methods: With IRB approval, we conducted a survey study of U.S.-based Hematology/Oncology (H/O), Radiation Oncology (RO), and Surgical Oncology (SO) members of the American Society of Clinical Oncology who completed CTR training. Data was anonymized and collected through Research Electronic Data Capture (REDCap). Outcomes were compared using Chi-square test for frequency data. Results: We received 225 survey responses (62.1% H/O, 23.3% RO, 13.2% SO, 1.4% others). About 28.4% (n = 64) of the respondents had a PhD or Master's degree in CTR (Group A) compared to 71.6% (n = 161) with graduate certificates or non-degree granting courses in CTR (Group B). Specialty ratio was equally distributed between both groups. Overall, 79.7% vs 57.5%; P < 0.001 of respondents worked in academia, of which 55.2% had tenure track positions. Over 49 different CTSA Programs throughout the U.S. were represented. In terms of impact with new research projects, the ability to secure funding and opportunities for multidisciplinary collaboration, satisfaction with CTR training was higher among Group A compared with Group B (P < 0.001; P < 0.01; P < 0.01 respectively). In terms of research output, higher satisfaction was seen in Group A (67.2% vs 47.4%; P < 0.01), however total publications per year were not statistically significant (P = 0.135). Usefulness of a CTR degree on career advancement, a difference of 50.0% vs 19.1%; P < 0.001 was noted. Similarly, usefulness regarding new job opportunities and return-on-investment also favored Group A (P < 0.001). Overall satisfaction with training was significantly higher in Group A (73.4% vs 48.7%; P = 0.004). Conclusions: This study is the first to report satisfaction ratings for CTR training among oncology specialties. Although no significant difference was observed in terms of publication output, those with higher levels of advanced degrees were more satisfied with their CTR training, and viewed it as more impactful to career advancement and research productivity. The evidence presented is useful for informing career development for oncology residents and fellows offered CTR degrees during their training.