bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of pre-infection routine laboratory parameters for COVID-19 mortality in tumor patients: Results of the ADHOK Coronavirus Tumor Registry.
Authors: Roesch Romina , Suedhoff Thomas , Wendtner Clemens M. , Kullmann Frank , Kubin Thomas , Schaich Markus , Mueller-Naendrup Clemens U. , Augustin Marinela , Hartmann Frank , Illerhaus Gerald , Hebart Holger Frithjof , Seggewiss-Bernhardt Ruth , Graeven Ullrich , Naumann Ralph , Kiani Alexander
Published: June 2021

10571

Background: Tumor patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection. However, they represent a heterogeneous group of individuals with variable risk. Identification of vulnerable subgroups is important for prioritization of vaccination strategies and possible early therapeutic intervention after infection. Methods: Tumor pts. with PCR-confirmed SARS-CoV-2 infection were included in the multicentric ADHOK registry by 22 institutions. Detailed information about tumor disease and treatment, as well as routine laboratory parameters determined at least 10 days prior to SARS-CoV-2 infection, was collected retrospectively. The primary endpoint was defined as the outcome of the SARS-CoV-2 infection, graded according to the WHO: asymptomatic, mild, moderate, severe, critical, and COVID-19-related death. Results: Until Feb. 5, 2021, 215 pts. (67% with solid tumors, 33% with hematological neoplasms) were included in the registry. 74% of the pts. had an active malignancy. The course of SARS-CoV-2 infection was rather variable: 66% of the pts. remained asymptomatic or showed a mild-to-moderate course, while the rest developed severe or critical disease. The COVID-19-related mortality rate was 24%. Pre-infection routine laboratory values were available for 104 pts., obtained at a median of 21 days before SARS-CoV-2 infection. Compared to COVID-19 survivors, COVID-19 non-survivors showed significantly higher median levels of absolute neutrophil count (ANC: 3.6 vs. 6.4 /nL; p = 0.006, n = 91), neutrophil-to-lymphocyte ratio (NLR: 2.2 vs. 7.2; p = 0.005, n = 75), C-reactive protein (CRP: 9.9 vs. 42.0 mg/L; p = 0.001, n = 104), and lactate dehydrogenase (LDH: 213.0 vs. 267.0 U/L; p = 0.016, n = 78). When categorized by a median split, COVID-19 mortality was significantly higher in pts. with ANC > 4.4 /nL (4% vs. 55%, p < 0.001), NLR > 4.1 (5% vs. 58%, p < 0.001), CRP > 15.4 mg/L (18% vs. 46%, p = 0.003), LDH > 236 U/L (15% vs. 49%, p = 0.003) and lymphocytes < 1.3 /nL (41% vs. 11% p = 0.002). In multivariable analysis, ANC and CRP showed a strong and significant association with COVID-19-related death (OR 23.0 and 7.7, p = 0.007 and 0.029, respectively). To develop an easy-to-apply pre-infection score, we combined ANC and CRP and were able to separate three groups of pts. with significantly different COVID-19 outcomes (p < 0.001) (Table). Conclusions: Our results unveil subgroups of tumor pts. who may be at increased risk of severe COVID-19 and point to pre-infection routine laboratory parameters with potential prognostic power: ANC and CRP may help identify pts. at risk for severe COVID-19 before SARS-CoV-2 infection.[Table: see text]
Incidence and trend of Epstein-Barr virus-related cancer: A surveillance, epidemiology, and end results program based study.
Authors: Shen Jiayi , Luo Meijuan , Liu LiTing , Chen Qiu-Yan , Tang Lin-Quan , Mai Hai-Qiang
Published: June 2021

10575

Background: Epstein-Barr virus (EBV) infection was highly prevalent, as was found in more than 90% of the adults globally. EBV infection has been found to be related with several types of cancer and classified as group 1 carcinogen by the International Agency for Research on Cancer. The association between EBV infection and malignancy was observed in Burkitt lymphoma (BL), Hodgkin lymphoma (HL), extranodal natural killer (NK)/T-cell lymphoma (NNKTL), gastric cancer (GC) and nasopharyngeal cancer (NPC). In this study, we aimed to analyze the incidence and the trend of incidence of these virus-related cancer and to identify whether the trend was similar between them. Methods: This was a retrospective analysis based on the data from Surveillance, Epidemiology, and End Results (18 registries, 2000-2017), which totally included 71,415 patients. EBV-related cancers were defined as BL, HL, NNKTL, GC and NPC. Age-adjusted incidence rates were displayed as per 100,000 persons. In terms of incidence trend, we calculated the average annual percent change (AAPC). AAPC was considered significantly different from 0 when the P-value was smaller than 0.05. The impact of the epidemiological and clinical characteristics on the incidence trend was estimated, with cancer type, histology, age, sex and race considered. Results: Incidence rates of EBV-related cancers were 6.68 per 100,000 persons in 2000 and 5.80 in 2017, of which the AAPC was -0.8 (95%CI, -1.1 - -0.5, P-value < 0.001). (Table) Similar with EBV-related cancer as a whole, the APCCs of BL, HL and GC were statistically significantly smaller than 0, except that the APCCs of NNKTL and NPC were statistically significantly larger than 0 and not statistically significantly different from 0 respectively. The incidence of EBV-related cancer also decreased in mixed cellularity classical HL, nodular sclerosis classical HL, adenocarcinoma of GC, signet ring cell carcinoma in GC, undifferentiated carcinoma of NPC, squamous cell carcinoma of NPC, patients diagnosed at the age of 20-39 years old and 60-79 years old, male patients and race as white, black or Asian, but increased in classical HL, NOS, nodular lymphocyte predominant HL and non-keratinizing carcinoma of NPC. Conclusions: Incidence of EBV-related cancer decreased during 2000 and 2017, which was consistent in BL, HL and GC.[Table: see text]
The lung cancer obesity paradox: An analysis of 432,924 patients.
Authors: Miles Brittany , Mackey James David
Published: June 2021

10578

Background: The lung cancer obesity paradox is the unexpected inverse relationship between body mass index (BMI) and lung cancer mortality. While there is a growing body of evidence to support the existence of the obesity paradox in lung cancer, little is known about its magnitude and relationship to cancer incidence and its impact on outcomes from surgery, chemotherapy, immunotherapy, and radiation treatment. Methods: To evaluate the impact of obesity on lung cancer incidence, we used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 69 Million patients in 49 large Healthcare Organizations. We evaluated 2 patient cohorts of 216,462 adult smokers aged 18 to 75 that were matched for age, race, gender, and ethnicity. One cohort of patients carried a diagnosis of overweight and obesity (ICD-10 code E66), while the other cohort required exclusion of those diagnoses. Results: We found a statistically significant decrease in lung cancer incidence for patients with obesity (1.407% vs 2.039%, p < 0.0001), in addition to superior overall survival (95.344% vs 92.039%, p < 0.0001). A subset analysis of patients who contracted lung cancer showed a statistically significant benefit in median survival in favor of patients with overweight and obesity (851 vs 602 days, p value 0.0009). Conclusions: These findings support the existence of the obesity paradox in lung cancer, and its positive impact on both lung cancer incidence and outcome.
Evaluation of proband adherence and satisfaction with a prospective cascade testing protocol.
Authors: Smith Maria , Hwang Kristina , Smith Julia Anne , Pothuri Bhavana
Published: June 2021

10593

Background: We sought to evaluate the feasibility of a Cascade Testing (CT) protocol for family members of probands with actionable germline mutations associated with endometrial or ovarian cancer. Here, we characterize proband compliance with contacting family members for CT and proband satisfaction/regret. Methods: In this prospective study, consenting patients with pathogenic germline mutations associated ovarian or endometrial cancer completed a demographic survey and were asked to contact first- and second-degree relatives with genetic testing results. After a 1–3-month period, probands completed a survey indicating how many relatives had been contacted. At 3 months following consent, probands were asked to complete the validated Impact of Event Scale (IES) and Decision Regret Scales (DRS). Characteristics of probands who contacted relatives and those who did not were compared. Results: The study has accrued 57 probands since opening in March 2019. Germline mutations identified in the 57 probands include 27 BRCA1 (47.4%); 21 BRCA2 (36.8%); 3 BRIP1 (5.3%); 2 MLH1 (3.5%); 2 MSH2 (3.5%); 3 MSH6 (5.3%); 3 PMS2 (5.3%); 1 EPCAM (1.8%); 1 RAD50 (1.8%). Twenty-four (42.1%) probands had a history of cancer (breast 12; ovarian 8; uterine 2; other 5). Of the probands, 32 (56.1%) completed follow-up questionnaires and 29 (50.9%) had contacted relatives about participating in CT. In total, 67 relatives were contacted. Probands contacted an average of 1 relative, ranging from 1-20. Of the 29 probands who contacted relatives, 13 (44.8%) completed IES and DRS questionnaires. The median IES score was 0 out of 75 (IQR 0.0-4.5) and the median DRS score was 0 out of 100 (IQR 0.0-11.3). When comparing characteristics of probands who contacted relatives with those who did not, those with annual household incomes <$75,000 were more likely to contact relatives vs those with incomes ≥$75,000 (77.8% vs 39.5%; p=0.01). There was no association between contacting relatives and personal cancer history, race/ethnicity, education status, or age (Table). Conclusions: Half of probands enrolled in this study contacted relatives about CT, and those with household incomes <$75,000 were more likely to contact relatives than those with higher incomes. Overall, probands reported little/no regret or distress after contacting relatives about genetic testing results.[Table: see text]
Assessing somatic and germline variants in cancer patients.
Authors: Ricker Charité , Amundson Erika , Algaze Sandra , Ciccone Marcia , Dong Stephen , D'souza Anishka , Felicetti Kimberly , Hernandez Daisy , Jayachandran Priya , Kang Irene , Narayanan Kavitha , Thomas Jacob Stephen , Tulpule Varsha , Umayam Rebecca , Xia Bing , In Gino Kim
Published: June 2021

10601

Background: The increasing integration of somatic and germline testing into oncology practice allows physicians to target oncologic therapy and identify those with cancer predisposition. We explored the impact of a somatic assay (liquid biopsy, LB) on the identification of patients appropriate for germline genetic testing. Methods: We identified a cohort of diverse cancer patients with LB to assess for targetable somatic gene variants at LAC+USC Medical Center between 2016 and 2020 (n= 467). To enrich the cohort for variants that may reflect germline findings, we focused on the 46 patients (9.9%) who had at least one variant identified with a cell-free DNA (cfDNA) fraction of 25.00% or greater. Retrospective chart review extracted demographics and medical history with variables related to cancer history and treatment. LB variants were classified based on whether germline confirmation was indicated and the results of germline tests, when done, were reviewed. Results: Table summarizes the characteristics of the 46 patients identified to have at least one variant on LB in ≤ 25% of the cfDNA. The most frequently mutated genes on LB were TP53 (n=18, 39%), KRAS (n=11, 24%), APC (n=8, 17%), BRCA2 (n=7, 15%), PIK3CA (n=6, 13.0%), and BRCA1 (n=4, 9%). Seventeen patients (40%) were referred for genetic counseling and 13 (30%) underwent germline testing of whom 10 (77%) carried pathogenic variants (PV). All germline PV were concordant with LB variants identified. Four patients with PV BRCA2 on LB and confirmed to be germline, had lung or biliary tract diagnoses, which are not part of the typical BRCA-tumor spectrum. Thirty-three patients were not referred for genetic counseling, though 24 (72%) had LB-identified variants in cancer predisposition genes and 18 (54%) merited a genetics referral. Among patients with germline mutations, three (23%) had targeted therapy and two (15%) had preventive surgery to address second primary cancer risk. Among the 467 patients with LB results, there were an additional 13 patients (not included in the enriched group) known to have a cancer predisposition gene PV. Only two (15%) had findings on LB reports that suggested germline testing would be indicated. Conclusions: While the purpose of somatic testing is to identify targeted therapy, it can provide germline insight, especially for patients not typically referred for genetic assessment. Further education and guidance is needed to assure that this aspect of somatic testing is appreciated by oncology providers and acted upon.[Table: see text]
Prospective genomic testing of unselected cancer patients yields insights about cancer susceptibility and noncancer disease with therapeutic implications.
Authors: Gray Stacy W. , McDonnell, MD, PhD Kevin , Idos Gregory , Hong Christine , Solomon Ilana , Sturgeon Duveen , Bonner Joseph D. , Smith Sidney A. , Morales Pichardo Jennifer , Woodhouse Melissa , Sobotka Elise , Zukin Elyssa , Courdy Samir , King Elisabeth , Xia Xiaoyu , Szelinger Szabolcs , LoBello Janine , Hamilton Stanley R. , Trent Jeffrey M. , Gruber Stephen B.
Published: June 2021

10603

Background: Clinicians have used strict criteria to determine eligibility for cancer susceptibility (CS) testing and have limited genetic assessment to cancer-related genes. However, half of all CS mutation carriers are missed by criteria-based testing and there may be an unrecognized opportunity to modify care for patients who have rare but actionable genetic disorders as defined by the American College of Medical Genetics (ACMG). With the aim of improving patient outcomes through precision genomics, we initiated an enterprise-wide program to offer somatic and germline sequencing to all patients. Methods: We offer consented patients clinical grade paired somatic & germline WES/ RNA seq and panel germline testing for cancer (156 genes) and ACMG disorders (59 genes). Results are reviewed by a Precision Oncology Tumor Board. Somatic results are returned by the treating team. Germline results are returned by phone (genetic counselor, GC) followed by a clinic visit (GC+MD) for those with pathogenic/likely pathogenic (P/LP) mutations and selected variants of uncertain significant. We evaluated the proportions of patients with somatic findings suggestive of germline conditions and those carrying P/LP mutations in CS and ACMG genes. Results: 1,804 patients enrolled and received somatic sequencing: 52% female; 51% non-Hispanic White/ 20% Hispanic White/ 18% Asian/ 4% Black/ 7% other; median age 64. Review of somatic data suggest that 14% have findings suggestive of germline conditions based on factors such as TMB, MSI, and young age. Of the patients offered germline testing, >95% opted to receive CS/ACMG results. To date, we have sequenced 684 patients for CS and 647 for ACMG. 18% of patients had P/LP mutations in CS genes and 4% had P/LP mutations in ACMG non-cancer genes (Table). Conclusions: Prospective somatic/germline sequencing of unselected cancer patients reveals tumor findings suggestive of germline disorders and identifies patients with CS and non-cancer genetic conditions. These findings highlight the promise of a comprehensive sequencing approach to help guide cancer treatment, management of unrecognized cancer risk and the need for concomitant management of rare disorders such as arrhythmogenic cardiomyopathy and susceptibility to adverse reactions with anesthesia.[Table: see text]
Mutant PPM1D and TP53 populate the hematopoietic compartment after peptide receptor radionuclide therapy (PRRT) exposure.
Authors: Singh Abhay , Mencia-Trinchant Nuria , Griffiths Elizabeth A. , Gupta Medhavi , Gravina Matthew , Tajammal Rutaba , Faber Mark G , Yan LunBiao , Sinha Eti , Hassane Duane C. , Guzman Monica L. , Iyer Renuka V. , Wang Eunice S. , Thota Swapna
Published: June 2021

10605

Background: Mutations in TP53 and PPM1D are putative drivers associated with therapy related-myeloid neoplasm (T-MN) and have been identified in pre-treatment blood samples obtained at the time of primary malignancy, predating clinically evident T-MN. Genomic analysis of patients(pts) who undergo leukemogenic therapies will help understand T-MN biology and devise risk mitigation strategies. PRRT (Lu 177) for neuroendocrine tumors is associated with enhanced risk of T-MNs. The mechanism for T-MN induced by PRRT is largely elusive due to the novelty of this drug. Methods: We analyzed initial (n=13) and serial blood samples (n=4) prior to and following PRRT for clonal mutations in order to elucidate the role of PRRT in exerting selective pressures on HSCs. Genomic DNA was analyzed using a targeted myeloid 100-gene panel and a variant allele frequency (VAF) cutoff 1% was used to call clonal hematopoiesis (CH). Results: Fifty-four percent pts had CH, despite relatively young age of cohort (median age 58 years, range 41-75) and minimal chemo-radiotherapy exposure; baseline characteristics and molecular profile of cohort is published [Singh et al. Blood 2020; 136 (Supplement 1): 35–36]. Serial sample analysis in 4 pts (Table 1) demonstrates that PRRT exposure is associated with clonal evolution and accompanying cytopenias in 75% (3/4) pts. Pt-1 (age 67) with normal baseline hemogram developed persistent cytopenias after PRRT, accompanied by emergence and expansion of mutant- PPM1D (m PPM1D; VAF 20%). These data suggest that cytopenias result from repopulation of the HSC compartment by m PPM1D cells. In Pts 2 and 3 (age 74 and 75), we note expansion of m TP53 and m PPM1D clones respectively, also associated with the development of cytopenias. Pt-4 was younger (age 59) and developed no cytopenias. Exposure to PRRT was associated with loss of m TET2 and m DDX41, possibly due to lack of clonal fitness of m TET2/DDX41 clones and the relatively young HSC microenvironment. Conclusions: We conclude that mutations in PPM1D and TP53 are clinically relevant, contribute to clonal cytopenias and may increase risk of future T-MN. The temporal association of m TP53 and m PPM1D expansion with PRRT exposure in our analysis suggests selection of these clones in response to PRRT-induced stress, outcompeting wild type and less therapy-resistant HSCs. Our study along with others will inform future efforts to strategize methods of surveillance and early detection for clonality assessment and chemoprevention, to reduce adverse effects of leukemogenic therapies.[Table: see text]
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.
The cognitive load of inpatient consults: A convergent parallel mixed methods study using the consult cognitive load instrument.
Authors: Brondfield Sam , Lee Kewchang , O'Sullivan Patricia
Published: June 2021

11027

Background: Consultation is crucial for inpatient care and a primary responsibility of fellows. Understanding the cognitive load associated with the complex skill of consultation would enhance fellow learning. The authors aimed to determine themes describing the fellow experience during consults, align these themes with Consult Cognitive Load (CCL) scores, and identify strategies to manage cognitive load. Methods: The authors studied 16 fellows using mixed methods. Fellows who accepted an invitation completed a consult followed by the CCL, a measure of cognitive load during consults, and an interview. Three authors conducted a thematic analysis. Member checks and triangulation with fellows supported theme trustworthiness. Subsequently, three authors rated the extent and cognitive demand of each theme expressed in each transcript. The authors measured interrater reliability and used Spearman correlation to describe the association of these ratings with CCL scores. The authors examined themes to identify strategies that educators might use. Results: Analysis revealed four themes: “nature and scope,” which conceptually aligned with intrinsic cognitive load (IL); “leveraging resources,” which had elements of both IL and extraneous cognitive load (EL); “extraneous factors,” which aligned with EL; and “drivers,” which aligned with germane cognitive load (GL). Interrater reliability for extent and demand ratings ranged from 0.57 to 0.79. The correlation between “nature and scope” and IL was 0.37, “extraneous factors” and EL 0.71, and “drivers” and GL 0.32. “Leveraging resources” did not correlate with IL (0.06) or EL (-0.09). Potential strategies based on themes included offering level-appropriate assistance to match IL, focusing the fellow’s attention to reduce EL, and providing succinct teaching to promote GL. Conclusions: This study provided deep insight into the fellow consult experience and suggested trustworthy strategies that educators can use to design and guide consult learning. The theme “leveraging resources” merits further exploration.
Oncology trainees’ perceptions and knowledge of therapeutic cannabis use.
Authors: Bindal Poorva , Patell Rushad , Elavalakanar Pavania , Dodge Laura , Freed Jason , Rangachari Deepa , Buss Mary K. , Schonberg Mara A. , Braun Ilana
Published: June 2021

11028

Background: Evidence shows that cancer patients are interested in learning about medicinal cannabis and frequently ask their oncologists for recommendations. To determine whether oncology training is adequately preparing physicians to address this topic, we conducted a national survey of oncology trainees to determine attitudes, practices, and knowledge about medical cannabis in cancer care. Methods: An interdisciplinary team developed an electronic questionnaire assessing trainees’ current practices regarding cannabis recommendations in cancer care and their knowledge of its effectiveness and risks compared with conventional care for cancer-related symptoms. We contacted 155 oncology training programs throughout the U.S. and asked that they distribute the survey to their trainees. Primary outcomes were: whether trainees reported discussing or recommending cannabis with/to patients and whether they felt sufficiently informed to make such recommendations. We presented data as proportions and used chi-square tests to compare proportions between groups. Results: Forty training programs from 25 states participated; of the 462 trainees in these programs, 187 completed surveys, yielding a response rate of 40%. Of the participants, 52% were female, 53% White, 33% Asian, and 5% Hispanic. One third (34%) graduated medical school before 2015, and 22% attended medical school outside the US. While 24% of trainees reported having received training regarding medical cannabis, only 12% felt sufficiently informed to make cannabis recommendations. Despite this, 91% reported having discussed cannabis with patients, and 58% reported recommending cannabis clinically to more than five patients in the prior year. Many viewed it as useful adjunctive therapy that was at least as effective as conventional treatments for: anorexia/cachexia (72%), nausea/vomiting (45%), and pain (41%). Over half (55%) believed that cannabis was beneficial to patients at the end of life; 31%, patients in active treatment; 11%, cancer survivors; 20%, the elderly with cancer and 16%, young adults with cancer. Peer-reviewed material (30%), lectures or webinars by another physician (29%), and patients and their families (22%) were the most commonly cited sources of information regarding medical cannabis. Oncologists who reported at least one area of focus as supportive/palliative care were more likely to feel sufficiently informed to make recommendations than oncologists without this focus (17% vs. 4%, P = 0.01); no other demographic or practice characteristics were associated with feeling sufficiently informed (all P > 0.10). Conclusions: Although most oncology trainees discuss cannabis use with their patients, the majority do not feel sufficiently informed about its use in cancer care. This represents an unmet need in contemporary oncology training, trainee satisfaction, and patient care.