tbuckley/cabot-search huggingface dataset:
Evaluation of PSA progression after initiation of enzalutamide or abiraterone: Real-world data on metastatic castration-resistant prostate cancer (mCRPC).
Authors: Fernando López-Campos, David Lorente, Casilda Llacer Perez, Miguel Ramirez-Backhaus, Paula Peleteiro, Alfonso Gomez-Iturriaga, Ivan Henriquez-López, Rebeca Lozano, Nuria Romero, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Joaquin Navarro-Castellón, Ana Castaño, Lira Pelari, Antonio Hernández-Corrales, Virginia Morillo, Raquel García, Carlos Ferrer Albiach, Elena Castro, David Olmos
Journal: Journal of Clinical Oncology (2021)

5024 Background: PSA value is widely used for the monitoring of treatment outcome in mCRPC in the clinical real-world setting. Early PSA changes are not considered in the definition of PSAProg due to the potential for spurious “flare” reactions. We aimed to evaluate the significance of an early PSA increase in mCRPC patients (pts) treated with enzalutamide or abiraterone (Enz/Abi). Methods: We retrospectively evaluated Enz/Abi-treated mCRPC pts from 11 hospitals between 2011-2020. Early PSAProg was defined as a 25% increase in PSA from baseline at 4 (PSAProg4) or 8 (PSAProg8) weeks after treatment initiation. PSA progression at 12 weeks (PSAProg12) was confirmed by a second reading. Uni- and multivariable (MV) Cox regression models were conducted to explore the association of PSAProg and overall survival (OS) in chemotherapy naïve patients treated with Abi or Enz. Interaction tests were conducted to explore differences in the impact of PSA progression on OS in Abi or Enz-treated pts. Results: We analyzed 511 chemotherapy-naïve mCRPC pts treated with Abi (N=391; 76.5%) or Enz (N=120; 23.5%). Median follow-up: 30.2 months. OS was longer in Enz-treated pts (38.1 vs 29m; HR 1.4; p=0.027). 59 (15.1%), 70 (17.9%) and 48 (12.3%) of Abi-treated and 9 (7.5%), 11 (9.2%) and 10 (8.3%) of Enz-treated pts experienced PSAProg4, PSAProg8 and PSAProg12, respectively, although differences were not statistically significant. PSAProg was associated with worse OS at all 3 timepoints only in Abi-treated pts. In Enz-treated pts, PSAProg4 had a large impact on OS, not observed in PSAProg8 or PSAProg12. We observed no significant interaction between agent (Enz/Abi) and PSA progression (Table). Conclusions: PSA progression at 4 weeks after Enz/Abi is significantly associated with shorter OS and may help identify pts not benefitting from Abi/Enz before clinical or radiographic progression. PSA pattern progression and its association with OS might differ depending on the drug used (Enz/Abi). Prospective validation studies are needed.[Table: see text]
Overall survival (OS) and prognostic factors (PF) of patients (pts) with metastatic solid tumors admitted in intensive care unit (ICU).
Authors: Segolene Hautecloque-Raysz, Marie Albert Thananayagam, Niels Martignene, Marie-Cecile Le Deley, Nicolas Penel, Aurelien Carnot
Journal: Journal of Clinical Oncology (2021)

e24074 Background: Admission of cancer pts in ICU is a medical and ethical challenge, since there is no reliable prognostic tool for guiding decision making. Therefore, recent progress in cancer management improved the OS of advanced cancer pts, rendering this issue more and more frequent. Methods: We have retrospectively analyzed the medical charts of 129 consecutive pts treated in our institution and admitted in ICU from 01/2014 and 04/2019. We identified PF using Cox Models. We analyzed PF for OS or for ability to restart systemic treatment. Results: At the time of ICU admission, the mean age was 58.9 (range, 25-81). The were 51% of men. PS were 0-1 in 61% and 2-3 in 39%. The most prevalent cancers were lung (20%), sarcoma (17%), breast (16%) and gynecological cancers (11%). The number of metastatic sites was 1 (17%), 2 (39%), 3 (26%) and more (19%). The malignancy was stable in 69% and progressive in 31%. Pts currently received systemic treatment in 78%, were free of treatment in 5% and were not yet treated in 16%. Cancer itself (53%), toxicity of treatment (43%) and underlying comorbidities (37%) contributed to ICU admission. The number of organ failures was 0 in 12%, 1 in 40%, 2 in 26% and 3 or more in 22%. The 4 most symptoms were dyspnea (34%), severe infection (25%), cardiac event (23%) and bleeding (10%). Pt management required vasoamines administration (38%), ventilation (31%) and dialysis (4%). The median duration of stay in ICU was 4 days (range, 0-71). 21 (16%) pts died in ICU and 16 (12%) just after ICU discharge. 83 pts returned to home (64%). Systemic treatment was done in 61% of pts who left hospitalization alive after ICU. 1-month, 6-month and 12-month OS were 67, 36 and 21%, respectively. Multivariate analysis identified the following PF for OS: PS = 0 (HR = 0.57 [0.38-0.79]; p = .007), admission related to underlying comorbidity (HR = 0.63 [0.41-0.98], p = .0001) or admission related to treatment toxicity (HR = 0.31 [0.17-0.56] p = .0001). Multivariate identified 1 PF for ability to restart systemic treatment: one or less organ failure (HR = 0.34 [0.14-0.83], p = 0.02). Conclusions: In ICU, OS of adult pts with solid tumors looks like the non-cancer population. ¼ of admitted pts died in ICU or just after. Key PF were PS and cause of critical state. When ICU admission is related to cancer itself, the prognosis was poor.
Effect of Bacillus Calmette-Guerin (BCG) exposure on severity of COVID-19 infection: A COVID-19 and Cancer Consortium (CCC19) study.
Authors: Andrew Lachlan Schmidt, Ziad Bakouny, Chris Labaki, Babar Bashir, Jessica M. Clement, Natasha Catherine Edwin, Daniel Blake Flora, Jennifer Girard, Shuchi Gulati, Clara Hwang, Chinmay Jani, Gilberto Lopes, Ruben A. Mesa, Gil Redelman-Sidi, Sanjay Mishra, Jeremy Lyle Warner, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2021)

4529 Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers; it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associated with broad protection against viral pathogens, BCG exposure through vaccination or intravesical therapy may modulate host immunity and reduce the severity of COVID-19 infection. We report the effect of BCG exposure on COVID-19 severity in oncology patients from the CCC19 registry. Methods: The CCC19 registry (NCT04354701) was used to identify patients with prior BCG exposure. Cohort A received intravesical treatment for bladder carcinoma, and cohort B received prior BCG vaccination. Each cohort was matched 3:1 to non-BCG-exposed controls by age, sex, race, primary cancer type, cancer status, ECOG performance status (PS) and calendar time of COVID-19 infection. The primary endpoint was COVID-19 severity reported on an ordinal scale (uncomplicated, hospitalized, admitted to ICU +/- ventilated, died within 30 days) of patients exposed to prior BCG compared to matched non-exposed controls. 2-sided Wilcoxon rank-sum tests were used. Results: As of 6-Feb-2021 we included 124 patients with BCG exposure, 68 patients with bladder carcinoma who had received intravesical BCG (Cohort A), and 64 cancer patients with prior BCG vaccination (Cohort B). Median age was 76 years, IQR 69-83 (Cohort A) and 67 years, IQR 62-74 (Cohort B). Bladder cancer pts were predominately male (78%) vs 55% for Cohort B. Patients with PS 2+ were uncommon, 18% in Cohort A and 16% in Cohort B. COVID-19 illness severity was no different in patients exposed to prior intravesicular BCG (p=0.87). COVID-19 illness severity was no different in patients exposed to prior intradermal BCG vaccination (p=0.60). Conclusions: Despite this being the largest such cohort reported to date, we failed to demonstrate an association of prior BCG exposure with modulation of severity of COVID-19 illness. Prospective trials evaluating the protective effect of BCG vaccination are ongoing and will add further insight into the effect of BCG on COVID-19 illness.[Table: see text]
AFT-16: Phase II trial of neoadjuvant and adjuvant atezolizumab and chemoradiation (CRT) for stage III non-small cell lung cancer (NSCLC).
Authors: Helen J. Ross, David E. Kozono, James John Urbanic, Terence Marques Williams, Carter DuFrane, Ilze Bara, Katja Schulze, Jane Michelle Brockman, Xiaofei F. Wang, Junheng Gao, Everett E. Vokes, Tom Stinchcombe
Journal: Journal of Clinical Oncology (2021)

8513 Background: A minority of the approximately 40,000 US patients diagnosed annually with stage III NSCLC can be cured by concurrent CRT. Standard adjuvant immune checkpoint inhibitors (ICI) improve outcome for those patients who complete CRT with good performance status (PS) and without disease progression, but most patients diagnosed with unresectable stage III NSCLC will not meet the criteria for adjuvant ICI. AFT-16 investigated safety and efficacy of neoadjuvant and adjuvant atezolizumab as a strategy that may allow more patients to benefit from ICI. Methods: Eligible patients received 4 cycles (cy) of atezolizumab 1200 mg IV q 21 days followed by CRT with 60 Gy + weekly carboplatin and paclitaxel (CP), CP consolidation and adjuvant atezolizumab to complete 1 year of therapy (17 cy). The primary endpoint of disease control rate at 12 weeks (wks) has been reported. Secondary endpoints reported here include overall response rate, safety, and progression-free and overall survival (PFS, OS) measured from the start of induction therapy. Correlative science data and quality of life endpoints will be reported elsewhere. Results: 64 patients with unresectable stage III NSCLC, PS 0-1 and no active autoimmune disease or significant organ dysfunction were enrolled at 13 Alliance for Clinical Trials in Oncology sites from 11/2017 to 7/2019. 62 patients who received at least one dose of atezolizumab are included in this analysis. Median age was 63.9 years (range 38.1-86.5). Patients were 51.6% female, 77.4% white, 88.7% current &amp; former smokers and 56.5% PS 0. All patients are off study treatment. Mean cycles of treatment received was 9 (1-17). 46 patients were alive at median follow up 24.1 mo (range 3 – 34.1 mo). PFS at 12 and 18 mo from start of induction atezolizumab was 66% (95%CI 55-79) and 57% (95%CI 45-71) respectively. Median PFS was 23.7 mo (95%CI 13.2-NE). OS at 18 mo was 84% (95%CI 75-94). Median OS is not yet estimable. Atezolizumab was well tolerated. One grade (gr) 4 Guillain-Barre syndrome and 1 each gr 3 pneumonia, pneumonitis and colitis were attributable to neoadjuvant atezolizumab. The remaining 9 severe adverse events were unrelated to ICI. Conclusions: Atezolizumab prior to and following CRT for stage III unresectable NSCLC was well tolerated with encouraging PFS and OS without unexpected safety signals. Analysis of correlative endpoints and quality of life are ongoing. Further study of induction atezolizumab is warranted in patients with unresectable stage III NSCLC. Support: https://acknowledgments.alliancefound.org ; Clinical trial information: NCT03102242.
Heart Rate as a Marker of Relapse During Withdrawal of Therapy in Recovered Dilated Cardiomyopathy
Authors: Brian P. Halliday, Ali Vazir, Ruth Owen, John Gregson, Rebecca Wassall, Amrit S. Lota, Zohya Khalique, Upasana Tayal, Richard E. Jones, Daniel Hammersley, Antonis Pantazis, A. John Baksi, Stuart Rosen, Dudley J. Pennell, Martin R. Cowie, John G.F. Cleland, Sanjay K. Prasad
Journal: JACC Heart Failure (2021)

The objective of this study was to determine the relationship between heart rate and relapse among patients in the TRED-HF (Therapy withdrawal in REcovered Dilated cardiomyopathy trial). Understanding markers and mechanisms of relapse among patients with recovered dilated cardiomyopathy (DCM) may enable personalized management. The relationship between serial heart rate measurements and relapse was examined among patients in the TRED-HF trial, a randomized trial which examined the safety and feasibility of withdrawing heart failure therapy from 51 patients with recovered DCM over 6 months. In total, 25 patients were randomized to therapy withdrawal and 26 to continue therapy, of whom 25 subsequently began therapy withdrawal in a single arm crossover phase. The mean ± SD heart rate for those who had therapy withdrawn and did not relapse was 64.6 ± 10.7 beats/min at baseline and 74.7 ± 10.4 beats/min at follow-up, compared to 68.3 ± 11.3 beats/min at baseline and 86.1 ± 11.8 beats/min at follow-up for those who relapsed. After adjusting for differences in heart rate at baseline, patients who had therapy withdrawn and relapsed had a 10.4 beats/min (95% CI: 4.0–16.8) greater rise in heart rate than patients who had therapy withdrawn and did not relapse (P = 0.002). After data were adjusted for age, log N-terminal pro–B-type natriuretic peptide, and left ventricular ejection fraction (LVEF), heart rate (per 10 beats/min; hazard ratio [HR]: 1.65; 95% CI: 1.10-2.57; P = 0.01) and change in heart rate from baseline (per 10 beats/min; HR: 1.70; 95% CI: 1.12–2.57; p = 0.01) were associated with relapse. The results remained qualitatively the same after adjusting for beta-blocker dose. For patients with DCM and improved LVEF, the rise in heart rate after treatment is withdrawn treatment identifies patients who are more likely to relapse. Whether the increase in heart rate is a marker or a mediator of relapse requires investigation. (Therapy withdrawal in REcovered Dilated cardiomyopathy trial [TRED]; NCT02859311)
Satisfaction with care and attention to salient concerns by race in a diverse national sample of young women with breast cancer.
Authors: Bridget Rose Carroll, Yue Zheng, Kathryn Jean Ruddy, Karen Emmons, Ann H. Partridge, Shoshana M. Rosenberg
Journal: Journal of Clinical Oncology (2021)

e18561 Background: Young women with breast cancer (BC) have unique issues, including fertility, genetic, and emotional health concerns; these may sometimes be inadequately addressed by providers. Given documented disparities in BC care and outcomes, we sought to explore whether provider attention to these issues differs by race, as well as to examine racial differences in satisfaction with care among young patients with BC. Methods: The Young &amp; Strong Study was a cluster randomized trial of an educational and supportive care intervention at 14 academic + 40 community oncology practices across the US enrolling women with newly diagnosed BC at age ≤45 and their providers. Patients completed surveys at baseline, 3, 6, and 12 months after enrollment. Race was self-reported at baseline. Provider attention to fertility, genetics, and emotional health was evaluated by medical record review. The proportions of patients with attention to these concerns by 3 months was compared by race (white, Black, Asian, multi-racial/other/unknown) using Fisher’s exact tests. Satisfaction with care was assessed with the Patient Satisfaction Questionnaire-18 (PSQ-18) at 3 months. Median scores for each of 7 PSQ-18 subscales (1-5 scale, higher scores=more satisfaction) were compared by race with the Kruskal-Wallis test. Results: 465/467 (99.6%) of enrolled patients had evaluable data. 77% were white, 12% Black, 4% Asian, and 7% multiracial/other/unk. Median age at diagnosis was 40 (range: 22-45) years. Provider attention to genetics (≥85%) and emotional health (≥90%) was high across groups, and there were no differences by race in attention to fertility, genetics, or emotional health (Table). Among 359/465 women (77%) who completed the PSQ-18, median subscale scores ranged from 3.5-4.5, indicating high levels of satisfaction with care. For the PSQ-18 technical quality domain, median scores were lower (p=.03), indicating less satisfaction, in Black and Asian women (4.0) and higher in white women (4.5). Median scores for other PSQ-18 domains (general satisfaction, interpersonal manner, communication, financial, time spent with doctor, accessibility) did not differ by race. Conclusions: Satisfaction with care was high and issues related to fertility, genetics and emotional health were addressed by providers in the majority of young women in our study, with minimal differences by race. These patients were all enrolled in a clinical trial and had access to high-quality care, limiting the generalizability of our findings. Larger, population-based studies in more diverse settings are warranted. Clinical trial information: NCT01647607. Attention to psychosocial concerns by race. [Table: see text]
Gene set enrichment analysis for genome-wide DNA methylation data
Authors: Jovana Maksimovic, Alicia Oshlack, Belinda Phipson
Journal: Genome biology (2021)

Abstract DNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalization, and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches, and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.
Real-world overall response rate and other outcomes related to originator and biosimilar rituximabin patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma in the United Kingdom.
Authors: Ali McBride, Shoshana Daniel, Maurice T. Driessen, Agota Szende, Azhar Choudhry, Marc Tian, Rinat Ariely, Stephen Thompson
Journal: Journal of Clinical Oncology (2021)

e18696 Background: Rituximab is a chimeric anti-CD20 monoclonal antibody therapy, used primarily for treating chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Rituximab-abbs, the first rituximab biosimilar, was approved in the UK in 2017 and was expected to significantly reduce drug acquisition costs, but there is a lack of real-world evidence regarding patient outcomes with rituximab-abbs. This non-interventional study assessed the real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. Methods: Anonymized data on patient characteristics, response to treatment, healthcare resource utilization and costs were abstracted retrospectively via an online physician survey. UK-registered hematologists and oncologists reported on randomly selected patients aged ³18 years from four cohorts with documented CLL or NHL, who had received rituximab-abbs or rituximab as first-line immunotherapy (between January 1, 2018 and June 30, 2019). Patient outcomes data were provided from first treatment to the last date of follow-up available in the medical records. Results: In total, 46 physicians abstracted data from 201 patient charts. Demographic profiles of the cohorts were similar. For both treatments, the overall response rate (ORR) was very high for patients with CLL or NHL (Table) along with rates for six-month progression-free survival (96–98% across cohorts) and one-year survival (98–100% across cohorts). Most patients did not experience a grade ≥3 adverse event during treatment (54–66% across cohorts); the most common grade ≥3 adverse events were neutropenia, fatigue, anemia and infusion reactions. Healthcare resource utilization was similarly high across cohorts, driven by drug costs, diagnostic testing, oncologist office visits, and day case hospital admissions. Mean annual savings of approximately £1,000 per patient were seen with rituximab-abbs, attributable to first-line treatment costs. Conclusions: The originator (rituximab) and biosimilar (rituximab-abbs) products yielded comparable efficacy and tolerability in treating CLL and NHL in routine UK clinical practice, with rituximab-abbs demonstrating cost-savings. These findings should inform decision-makers on the potential for cost reductions where the biosimilar rituximab-abbs is available as a treatment alternative.[Table: see text]
RARE-13. PRIMARY EMPTY SELLA SYNDROME AND PSEUDO-TUMOR CEREBERI: CORRELATION OF ASSOCIATION AND SURGICAL PLAN
Authors: Mohamed Arnaout
Journal: Neuro-Oncology (2021)

Abstract Introduction Management of primary empty sella syndrome (ESS) is generally remaining a neurosurgical challenge due to lack of a well standardized approach. Pseudo-tumor cereberi (Benign or idiopathic intracranial hypertension) is commonly associated condition. In this study, we have demonstrated the relationship and surgical plan and outcome of such cases. Patients and Methods: We retrospectively studied 24 patients with primary empty sella syndrome (ESS) for two years who were diagnosed radiologically as ESS. Fundus and other ophthalmological examinations were done. Lumbar puncture and cerebrospinal fluid (CSF) manometer were evaluated in those with papilledema. All patients’ data were collected and analyzed. Results Basically, 24 patients (18 females and 6 males) were radiologically diagnosed as EES. 13 females and only one male were having symptoms of BIH. 17 patients (70.83%) had headache as the first presentation. Second most common presentation in our study was visual in 14 patients (58.3%). Two patients (8.3%) had pituitary hypersecretion namely; growth and prolactin hormones. In those (58.3%) confirmed to have BIH Theco-peritoneal shunts were inserted. Incidental cases (29.17%) without symptoms were followed up. Conclusion Although (ESS) is a well-known radiological hallmark for BIH, in our study not all patients had BIH. Interestingly, pituitary hyperfunction may be the first presentation in some rare cases. Generally, natural history of that entity was benign. Frequent follow-up by neurosurgeons and increased awareness of associations are advised. We believe a more prospective large number cohort is important to outline the natural history.