tbuckley/cabot-search huggingface dataset:
The association of <i>ATM</i> alterations with clinical and molecular features in metastatic castration-resistant prostate cancer.
Authors: Guo Xi, Qing WANG, Qin Zhang, Qianqian Duan, Yaqin Liu
Journal: Journal of Clinical Oncology (2021)

e17019 Background: Ataxia telangiectasia-mutated（ATM）is a serine/threonine kinase involved in DNA-damage repair (DDR) system and regulating cell cycle checkpoints, senescence, and apoptosis. Several clinical studies provide evidence about the DDR-mutated metastatic castration-resistant prostate cancer (mCRPC) benefit from PARP inhibitors (PARPi). However. the efficacy of PARPi was limited for mCRPC patients harboring ATM aberrations. We aimed to determine the association of ATM mutations with clinical and molecular features in patients with mCRPC. Methods: A total of three independent prostate cancer cohorts (MCTP, N = 61; SU2C-PCF, N = 429; MSKCC, N = 451) were used for analysis. We selected patients with characteristics “mCRPC” and “histology type: prostate adenocarcinoma”. Both the somatic and germline pathogenic alterations were analyzed, including single nucleotide variations (SNVs), in-frame insertions or deletions (Indels), frameshifts, homozygous deletions and fusions. The statistical analysis was conducted by R software (v.3.6.2). Results: We merged the three mCRPC cohorts, generating a new cohort consisting of 507 mCRPC patients. The median age was 62 (range, 38.6-89). The number of biopsies was 1-3 per patient. Of the 527 sequenced specimens, 39% were lymph node, 27% were bone, and 14% were liver. Forty percent of the patients had exposed to or on-treatment with next-generation androgen receptor signaling inhibitor (ARSI). A total of 44 patients (8.7%) harbored deleterious variations in ATM, including 10 homozygous deletions. The coexistence mutations were most commonly located in androgen receptor ( AR), followed by TTN/KMT2C/MUC16/TP53. Furthermore, we explored the association of pathogenic ATM alterations with clinical features. Compared with noncarriers of ATM mutations , carriers were diagnosed at a younger age (median: 59 vs 62.4, P = 0.022). In the subgroup from SU2C-PCF cohort, prostate specific antigen (PSA) at diagnosis and the proportion of Gleason score between 8-10 were analyzed, both showed no significant differences between the two groups. Notably, we observed a statistically significant higher TMB in ATM-altered group than ATM wildtype group (median, 2.04 vs 1.61, P = 0.013). Overall survival (OS) was not compared because of the limited clinical outcomes in ATM-mutated population. Conclusions: This study involving 3 cohorts identified the prevalence of pathogenic somatic or germline ATM mutations and explored the association of ATM alterations with both clinical and molecular features. Patients with ATM mutations tended to diagnose prostate cancer at an earlier age. Meanwhile, significantly higher TMB might imply potential immunotherapy opportunities in ATM-altered mCRPC without standard-of-care approaches.
A first-in-human phase I dose escalation of YH001, an anti-CTLA-4 monoclonal antibody (mAb) in combination with toripalimab (anti-PD-1 mAb) in patients with advanced solid tumors.
Authors: Vinod Ganju, Adam Cooper, Bo Gao, Kate Wilkinson
Journal: Journal of Clinical Oncology (2021)

2577 Background: YH001 is a humanized anti -hCTLA-4 IgG1 mAb that relieves CTLA-4-mediated immunosuppression, and thereby enhances the T-cell-mediated antitumor immune response. Pre-clinical data have shown potent anti-cancer activity when combined with anti-PD-1 mAb. Methods: This is an ongoing phase 1 dose-escalation study. Patients (pts) with advanced solid tumors received YH001 by IV administration at 0.05 to 6.0 mg/kg for 1 cycle (21 days) then in combination with Toripalimab (anti-PD-1 mAb) at 240 mg Q3W for 4 cycles. An accelerated titration method followed by the standard “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Results: As of 31-Dec-2020 data cut-off, 10 pts were enrolled and treated at 0.05 mg/kg (n = 2), 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3) and 1 mg/kg (n = 2). The median age was 62 years (range 46-74). Baseline ECOG scores were 0 (n = 8), 1(n = 2) with all pts progressed after a median of 2 prior lines of available standard therapy (range 1-4) including 1 pt progressed after immunotherapy of pembrolizumab. There were no dose limiting toxicities (DLT) observed. No severe adverse events (SAEs), Grade (G) 3 or above adverse events (AEs) and AEs leading to treatment discontinuation were reported. Twelve drug related AEs were all G1/2 events including 2 G2 AEs (1 rash maculopapular at 0.05mg/kg, 1 hypothyroidism at 0.1mg/kg), 10 G1 AEs (1 hypotension, 1 dry skin, 1 pruritus at 0.05mg/kg; 1 rash, 1 rash macular, 1 hyperthyroidism, 2 rash pruritus at 0.1mg/kg, 2 fatigues at 0.3mg/kg). Among 7 patients having imaging tumor assessment by RECIST v1.1, there were 4 SD, including 1 at 0.05 mg/kg with tongue carcinoma at week 8 assessment, 1 at 0.1 mg/kg with nasopharyngeal carcinoma at week 8 and 15 assessment, 2 at 0.3 mg/kg with gastroesophageal junction cancer and uterus leiomyosarcoma at week 8. Conclusions: YH001 combined with Toripalimab is safe and tolerable up to 1 mg/kg dose level. Updated safety and preliminary efficacy data will be presented. Clinical trial information: NCT04481009.
Metastasectomy versus radiation of secondary sites in stage IV breast cancer.
Authors: Nadeem Bilani, Leah Elson, Elizabeth Blessing Elimimian, Hong Liang, Diana Saravia, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2021)

1094 Background: Prospective trials have yielded mixed results on the utility of surgery in metastatic breast cancer (mBC). Thus far, however, studies have focused primarily on the impact of lumpectomy or mastectomy. We previously showed that a combined approach involving resection of primary and secondary sites (i.e. ‘metastasectomy’) in patients with limited mBC was associated with improved overall survival (OS). We sought to evaluate the effect on OS of two approaches to loco-regional therapy (LRT) at secondary sites: metastasectomy versus radiation therapy. Methods: This is a retrospective analysis of patients diagnosed with mBC from 2010-2017 using the National Cancer Database. We identified 5 cohorts of patients by site of metastasis: mBC involving only 1) bone, 2) brain, 3) liver, or 4) lung; and 5) patients with metastasis involving &gt;1 site. For each cohort, we used Kaplan-Meier (KM) models with log-rank testing to evaluate differences in OS, by the LRT approach at secondary sites (radiation versus metastasectomy). Prior to KM modeling, chi-squared statistics were used in each cohort to assess whether age, race, Charlson/Deyo score (CDS) for comorbidity, and receptor subtype were potential confounders of survival. The KM models were adjusted accordingly, as per the table below. Results: 53.4%) were between 50-70 years old, White (n=53,409, 78.9%), and had hormone receptor (HR)-positive/HER2 receptor-negative breast cancer. N=12,362 patients received radiation therapy at either the bone, brain, liver, or lung; while n=2674 underwent surgical resection of a metastatic site. Of patients with metastasis to 1 site (n=44,451), n=30,341(68.3%) involved the bone, n=1,119 (2.5%) involved the brain, n=5,227 (11.8%) involved the liver, and n=7,764 (17.5%) involved the lung. N=24,017 patients had metastatic disease involving &gt; 1 site. KM modeling revealed superior OS of patients undergoing metastasectomy versus radiation of secondary sites in all 5 cohorts (p&lt;0.05). The difference in median OS (ΔmOS) by LRT approach was more pronounced when metastasis involved only the liver (41.6 months) or lung (48.6 months), versus only the brain (9.7 months) or bone (8.7 months). Conclusions: Metastasectomy appears to confer a superior benefit for OS compared to radiation of secondary sites, particularly in patients with secondary site involvement limited to the liver or lung. More research is needed from prospective trials investigating surgical resection of metastatic sites.[Table: see text]
A nurse-led telephone triage for the prevention and control of COVID-19 spread in an oncology department.
Authors: Lorenzo Calvetti, Francesca Simionato, Alessandro Cappetta, Francesca La Russa, Roberta Cimenton, Barbara Gasparin, Francesco Corà, Giuseppe Aprile
Journal: Journal of Clinical Oncology (2021)

e13617 Background: After the results of the Nurse-led Telephone Triage (NTT) study ( Calvetti L, et al. ASCO 2020), the system has been implemented to prevent unnecessary hospitalizations of cancer patients. With the pandemic outbreak, a dedicated SARS-CoV-2 2019 (COVID-19) NTT protocol was added to monitor cancer patients (CPs) receiving active medical treatment. We report on the impact of NTT in limiting accesses and minimizing the risk of spread of the infection through the Department of Oncology. Methods: CPs on active medical treatment were educated to call the NTT in case of any symptoms suspected for COVID-19 infection to the Oncology Department of Vicenza, Italy, during the COVID-19 pandemic (February 22 2020 to January 31, 2021). Each event assessment was performed by trained oncology nurses with the supervision of a medical oncologist on duty and in case of suspected COVID-19 infection a testing pathway for COVID-19 was activated. Primary endpoint of this study was to compare incidence of COVID-19 and related deaths in both CPs on active medical treatment and health workers with the rate in the overall population of Veneto region. Results: From February 22 2020 to January 31, 2021 1,154 patients received systemic anticancer treatment (versus 1,022 patients in the same 2019 – 2020 period). Total consultations at NTT were 587; 97 patients reported symptoms suspected for COVID-19 infections. The COVID-19 testing pathway was launched in 60 CPs and a positive test was reported in 25 CPs (2.2% incidence compared to 6.5% in the overall Veneto region population). Two COVID-19 related deaths were reported (8% death rate). In the same period, 2/54 (3.7%) health workers tested positive for COVID-19. Patients who tested positive had a median treatment delay of 25 days. Conclusions: The NTT system in the clinical practice provided a useful tool for monitoring and limiting hospital-acquired COVID-19 infection among both CPs on active treatment and health workers.
The clinician educator career in oncology.
Authors: Meredith Elana Giuliani, Nishin Bhadkamkar, Sam Joseph Lubner, Michal Tibbits, Jennifer Tseng, Jamie H. Von Roenn
Journal: Journal of Clinical Oncology (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 &gt;50% of graduates), 59 (67%) of PDs/APDs reported &lt;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]
Health care disparities and barriers to palliative care among metastatic renal cell carcinoma patients: An NCDB analysis.
Authors: Janvi Wadiwala, Mausam Patel, Chenghui Li, Sanjay Maraboyina, Ahmed Safar, Thomas Kim
Journal: Journal of Clinical Oncology (2021)

4545 Background: Palliative care improves quality of life for both patients and caregivers but may be underutilized due to socioeconomic barriers to access. An NCDB analysis was performed to analyze the effect of socioeconomics on palliative care receipt among patients with metastatic renal cell carcinoma. Methods: A retrospective hospital-based analysis was performed using the National Cancer Database to identify variables that significantly affect receipt of palliative care among patients diagnosed with metastatic renal cell carcinoma diagnosed between 2004 and 2016. Sub-cohort analysis was also performed among patients with the most severe disease. Multivariate binominal logistic regression was performed to determine the association of underlying socioeconomics with receipt of palliative care. The odds of receiving palliative care based on socioeconomic factors was reported as odds ratios (OR) with 95% CI. Results: There were 50405 patients meeting inclusion criteria with 40448 (80.2%) undergoing no palliation and 9957 (19.8%) undergoing palliative care. Both Black and Spanish/Hispanic patients had decreased odds of receiving palliative care (OR, 0.816, 95% CI, 0.753 to 0.885 and OR, 0.599, 95% CI, 0.540 to 0.665, respectively). Increasing age, papillary histology, increasing income, and increasing distance were also significantly associated with decreased odds of receiving palliation while treatment at an integrated network cancer program or comprehensive community cancer program and higher educational attainment were associated with increased odds of receiving palliative care. Similar findings were demonstrated among patients with the most severe disease. Limitations include the retrospective design and potential underlying selection biases of this study. Conclusions: Significant associations between receipt of palliative care and socioeconomic factors exist among patients with metastatic renal cell carcinoma. In this study among patients with metastatic renal cancer, we found associations between socioeconomics and palliative care access including age, race, Spanish/Hispanic origin, income, education, and other factors.
Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy
Authors: Yinxian Yang, Shiyi Zuo, Linxiao Li, Xiao Kuang, Jinbo Li, Bingjun Sun, Shujun Wang, Zhonggui He, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe3+, trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe3+could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe2+generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H2O2, which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe3+/Fe2+ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.
Associations between longitudinal pretreatment BMI and neutrophil/lymphocyte ratio(NLR) and progression-free(PFS) and overall survival(OS) in advanced NSCLC patients treated with single agent anti-PD-1/anti-PDL1 monoclonal antibodies(mAbs).
Authors: Megan Randall, Sanjib Basu, Revathi Kollipara, Marta Batus, Philip D. Bonomi, Hita Moudgalya, Jeffrey Allen Borgia, Mary J. Fidler
Journal: Journal of Clinical Oncology (2021)

e21189 Background: Several parameters that have been associated with outcomes in patients with metastatic NSCLC treated with anti-PD1/PDL1 mAbs include tumor PD-L1 expression, tumor mutational burden, and baseline NLR. Further investigation into clinical correlates of benefit with immune checkpoint inhibitors remains an unmet need. Methods: The objective of this retrospective study was to examine the potential influence of pretreatment cachexia and chronic inflammation in patients with NSCLC that received second- or third- line single agent anti-PD1/PDL1 mAbs. Weight, BMI, and NLR, as well as longitudinal changes in these variables from at least six-weeks prior to initiation of treatment were correlated with progression-free and overall survival (PFS/OS). These associations were assessed using statistical methods for time-to-event analysis. Results: 192 patients were included: 59% female, 72% Caucasian, 18% African American, 79% current or former smokers. 185 patients had pretreatment NLR values and 63% and 42% had NLR ratios &gt; 3.5 and &gt; 5, respectively. 187 patients had pretreatment weight and BMI available. Of these, 63% had a loss in BMI prior to initiation of anti-PD1/PDL1 mAbs, 29% with &gt; 5% loss. Any BMI loss as well as BMI loss &gt; 5% over the time period prior to treatment initiation were associated with shorter PFS (p &lt; 0.01, 2.1 vs 4.37 mos for loss &gt; 5% vs ≤ 5%) and change in BMI assessed in continuous scale was also associated with PFS (HR = 0.94, p &lt; 0.05). Similarly, any BMI loss and BMI loss &gt; 5% were associated with shorter OS (p &lt; 0.01. 7.33 vs 12.23 mos for loss &gt; 5% vs ≤ 5%) and change in BMI and baseline BMI assessed in continuous scale were additionally associated with OS (HR = 0.97 and 0.94, p &lt; 0.05). Baseline NLR &gt; 5 was associated with shorter PFS (p &lt; 0.01) and baseline NLR assessed in continuous scale was negatively associated (HR = 1.01, p &lt; 0.05). Moreover, pre-treatment NLR &gt; 5 and baseline NLR &gt; 3.5 were associated with shorter OS (p &lt; 0.05). Pre-treatment NLR, baseline NLR, and %change in NLR, assessed in continuous scale, were negatively associated with OS (HR = 1.04, 1.02, 1.12, p &lt; 0.01). Conclusions: This retrospective study identified clinical features of NLR and BMI at treatment initiation and in the immediate pre-treatment period that were associated with PFS and OS on anti-PD1/PDL1 mAbs therapy. These parameters can easily be investigated in the front-line population. They may also have utility in identifying patients that would benefit from therapeutic strategies to reverse weight loss and inhibit immunosuppressive effects associated with elevated NLR in order to increase the effectiveness of immunotherapy.
Urinary biomarkers for monitoring treatment response in neuroblastoma patients.
Authors: Hizuru Amano, Akinari Hinoki, Hiroo Uchida, Kazuki Yokota, Takashi Ishigaki, Minoru Sakairi, Mayumi Abe, Yoshiyuki Takahashi, Atsushi Narita, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Aitaro Takimoto, Yoko Kano, Akihiro Yasui, Masamune Okamoto, Yoichi Nakagawa
Journal: Journal of Clinical Oncology (2021)

e22008 Background: Neuroblastoma is the most common extracranial solid tumor in children. Its heterogeneity may account for the non-uniform response to therapy; thus, accurate predictive biomarkers are required. We focused on urinary biomarkers since urine contains numerous low molecular weight metabolites that can be used as reliable and non-invasive biomarkers. We detected more than 2,000 metabolites by liquid chromatography-mass spectrometry (LC-MS) through a comprehensive analysis of metabolites in urine samples of patients with neuroblastoma and identified potential urinary biomarker candidates using the Wilcoxon rank-sum test and random forest. In this study, the levels of urinary biomarker candidates were compared between the responder and resistant groups to identify urinary biomarkers for monitoring treatment response. Furthermore, their effectiveness was compared with minimal residual disease (MRD) markers, which are currently considered to predict tumor relapse. Methods: Thirty-two patients with neuroblastoma were divided into two groups according to their responsiveness to therapy: the responder group, in which patients had no recurrence (60 urine samples from 24 patients) and the resistant group in which patients had a recurrence or died (18 urine samples from 8 patients). Levels of urinary metabolites (homovanillic acid [HVA], vanillylmandelic acid [VMA], 3-methoxytyramine sulfate [3-MTS], vanillactic acid [VLA], 3-methoxytyrosine [3-MTR]), and MRD markers (TH, PHOX2B, MK) were compared between the two groups during treatment. Results: The levels of five urinary metabolites (HVA, VMA, VLA, 3-MTR, 3-MTS) were significantly increased in the resistant group compared to that in the responder group. Conclusions: This study shows that three novel urinary metabolites (VLA, 3-MTR, 3-MTS) are significantly associated with the recurrence or death from neuroblastoma.
Prevalence of Proton Pump Inhibitor Use Among Patients With Cancer
Authors: Jean-Luc Raoul, Catherine Guérin-Charbonnel, Julien Edeline, Victor Simmet, Marine Gilabert, Jean-Sébastien Frenel
Journal: JAMA Network Open (2021)

This cross-sectional study evaluates the prevalence of proton pump inhibitor use among patients with cancer at 4 French comprehensive cancer centers.
Could SARS-CoV-2 cause tauopathy?
Authors: James Pratt, Evan Lester, Roy Parker
Journal: The Lancet Neurology (2021)

SARS-CoV-2 who have substantial neuroinflammation, and who are therefore potentially at a higher risk of developing secondary tauopathy, is unknown.It is also important to note that no direct causal link between COVID-19 and neurological or psychiatric sequelae has been found, and some complications-including anxiety disorders-might be due to the stress and trauma associated with social factors (eg, isolation) and treatment options (eg, intubation). 1 We believe that follow-up studies of neurological dysfunction in survivors of COVID-19 should be done, particularly in people who showed acute or subacute neurological symptoms.Such studies should persist for at least a decade and focus on young individuals (ie, those aged 30-40 years), to reduce the proportion of participants who will develop tauopathies because of old age.These studies should also investigate tau in blood or CSF, and tau aggregation by use of PET tracers.
Abstract 11967: Impact Of Prognostic Nutritional Index On Patients With Acute Myocardial Infarction
Authors: Takuya Ando, Kazuhiko Nakazato, Takatoyo Kiko, Takeshi Shimizu, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Background: Malnutrition has been known as a predictive factor of clinical outcome in patients with heart failure. However, the association between nutritional status and outcomes in patients with ...
Donor clonal hematopoiesis increases risk of acute graft versus host disease after matched sibling transplantation
Authors: Betül Oran, Richard E. Champlin, Feng Wang, Tomoyuki Tanaka, Rima M. Saliba, Gheath Al-Atrash, Guillermo Garcia-Manero, Hagop Kantarjian, Kai Cao, Elizabeth J. Shpall, Amin M. Alousi, Rohtesh S. Mehta, Uday Popat, Andy Futreal, Koichi Takahashi
Journal: Leukemia (2021)