tbuckley/cabot-search huggingface dataset:
Racial distribution of clinical trial participants in the United States.
Authors: Monaliben Patel, Lisa M. Hess, Eric Wen Su, Xiaohong Li, Debora S. Bruno
Journal: Journal of Clinical Oncology (2021)

e18516 Background: Lack of diverse representation in clinical trials negatively impacts the cancer survival of patients and populations unaccounted for in clinical research. Efforts such as the 1993 NIH Revitalization Act have focused on improving the diversity of trial participants in the US. This retrospective study evaluated the racial distribution of oncology clinical trial participants using data published in clinicaltrials.gov from Jan 2010 through Dec 2020. Methods: I2E of Linguamatics (IQVIA, Inc), a natural language processing software, was used to identify participant race in oncology trials. Data extracted included trial identifier, year of completion, sponsor, cancer type, and race. Studies were limited to academic, cooperative group and government studies headquartered in the US. Clinical trial results were compared to the racial distribution of SEER 2010 data using z-test. Results: Data from 35,686 patients (14,220 enrolled to 236 phase 2 and 21,471 enrolled to 47 phase 3 trials) were available for analysis. A summary by race is provided in the Table, excluding unknown, which represented 8.5% of phase 2 and 3.5% of phase 3 trials. The proportions of white/black patients enrolled to phase 2 and phase 3 trials beginning in 2010-12 were 84.4%/11% and 83.1%/9.9%, respectively (total enrollment 84.9%/9.6%). For trials beginning in 2015-17, white/black enrollment represented 88.5%/8.1% of patients enrolled to phase 2 and 86.4%/10.1% of patients in phase 3 trials. Black patients represented 9.6% of all trial participants, in contrast with the SEER data where 12% of all patients were black (p &lt; 0.001). For lung cancer trials, black participants represented only 7.9% of all trial participants whereas in breast cancer trials, 10.2% of participants were black, versus the SEER data specific to these tumor types (black patients represent 10.9%/11.5% of lung/breast cancer diagnoses between 2013 to 2017, both p &lt; 0.01). Conclusions: This study suggests that over the past decade most races (other than white) have been significantly underrepresented in US oncology clinical trials, and is even more pronounced for black patients with lung cancer. Based on this analysis, there is no evidence that trial enrollment distribution, particularly of white versus black participants, has changed since 2010. Data are limited to the relative lack of studies reporting results that began enrollment after 2017. These findings suggest that the development of new strategies to improve the recruitment of racial minorities to oncology clinical trials are warranted.[Table: see text]
Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma treated with R-CHOP.
Authors: Yan Qin, Haizhu Chen, Peng Liu, Changgong Zhang, Jianliang Yang, Lin Gui, Xiaohui He, Liqiang Zhou, Shengyu Zhou, Shiyu Jiang, Hongxin Jiang, Yuankai Shi
Journal: Journal of Clinical Oncology (2021)

e19549 Background: Unlike BCL2 translocation ( BCL2 TR ), limited data about the prognostic significance of BCL2 mutations ( BCL2 MUT ) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2 GA/AMP ) and BCL2 MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2 TR . As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2 GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P&lt; 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2 GA/AMP . By contrast, neither BCL2 MUT nor BCL2 TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2 GA/AMP , TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2 GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P&lt; 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P&lt; 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P&lt; 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P&lt; 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2 GA/AMP , and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.
A Pilot Study of Weekly Brentuximab Vedotin in Patients with CD30+ Malignancies Resistant to Every 3 Week Brentuximab Vedotin
Authors: Jacqueline N. Poston, Jonathan R. Fromm, Heather A. Rasmussen, Andrei R. Shustov, Edward N. Libby, Stephen D. Smith, Ted Gooley, Ajay K. Gopal
Journal: Blood (2017)
Association of inoperable glioblastoma with a heterogeneous functional and survival outcome.
Authors: Vincent Harlay, Anderson Loundou, Celine Boucard, Gregorio Petrirena, Maryline Barrie, Chantal Campello, Didier Autran, Laetitia Padovani, Dominique Figarella, Sebastien Boissonneau, Henry Dufour, Karine Baumstarck, Emeline Tabouret, Olivier L. Chinot
Journal: Journal of Clinical Oncology (2021)

e14036 Background: “Biopsy only” GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients (Kole, Cancer 2016). Our objective was to explore heterogeneity of inoperable GBM patients group, both for patients characteristics, pattern of care planned and completed, functional and survival outcome. Methods: Patients with inoperable GBM included in a prospective regional glioma cohort initiated in 2014 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. Functional independency analyzed as a cumulative time of KPS≥70, PFS and OS were analyzed. Results: Of 535 patients referred to our center, 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. 18 patients were excluded for missing data leaving 139 patients for the present analysis. 54 (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 3 were subsequently referred to RT), 17 (12%) referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, 69y for RT-TMZ, CT-UF, PC respectively); for KPS (70, 60, 50 for RT-TMZ, CT-UF, PC respectively); for mean tumor surface (793, 1420, 1412 cm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-CT and CT-UF respectively); for steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65-18.71), 8 months (95% CI, 4.62-7.67), 2 months (95% CI, 0.67-3.33) for RT-TMZ, CT-UF, PC respectively. Of importance, mean duration of functional independence was of 8.3 months, 2.1 months, and 0.1 month for RT-TMZ, CT-UF, and PC respectively; 33/139 (24%) of the patients experienced functional independency for more than 40% of their life time. Conclusions: Inoperable GBM constitute a large and heterogeneous population in which more than 1/3 of the patients are amenable to standard of care, with survival outcome similar to the one of patients who underwent surgery. Patients considered unfit for RT-CT at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome that deserve new effective treatments. Cumulative duration of functional independence is limited and should be considered as part of treatment evaluation.
Should we routinely screen for frailty prior to gynecologic oncology surgery? Frailty as a potential predictor of adverse postoperative outcomes in elderly patients.
Authors: Sarah Mah, Tharani Anpalagan, Maura Marcucci, Clare Reade, Waldo Jimenez, Lua Ruhiyyih Eiriksson, Vanessa Carlson, Millie Walker, Julie My Van Nguyen
Journal: Journal of Clinical Oncology (2021)

6517 Background: Frailty is increasingly recognized as an adverse prognostic factor of postoperative morbidity and survival in several surgical disciplines. There is no consensus on routine frailty screening in Gynecologic Oncology. Our goal was to evaluate the predictive role of the National Surgical Quality Improvement Program(NSQIP) comorbidity-based modified Frailty Index-5(mFI-5) in Gynecologic Oncology patients over the age of 70. Methods: Elective laparotomies between 01/2016-09/2020 at the Juravinski Hospital in Hamilton, ON were reviewed using prospectively-collected NSQIP data and chart review. Complication severity was assessed by Clavidien-Dindo classification. The primary outcome was rate of 30-day grade III-V complications. Secondary outcomes were: grade II-V complications, myocardial injury, length of stay(LOS), non-home discharge, and non-initiation/non-completion of adjuvant chemotherapy. Logistic regression analysis was performed. Survival analysis and receiver-operator characteristic curves are underway. Results: In this cohort of 259 patients, frail patients(mFI-5≥2) were at significantly greater risk of grade III-V complications (OR23.77, 95%CI 9.69-66.26, p &lt; 0.0001), grade II-V complications (OR3.8, 95%CI 1.96-7.85, p = 0.0002), myocardial injury (OR3.44, 95%CI 1.66-7.05, p = 0.0009), LOS≥5days (OR2.96, 95%CI 1.61-5.52, p = 0.0006), non-home discharge (OR7.37, 95%CI 2.81-20.46, p &lt; 0.0001), and non-initiation/non-completion of chemotherapy (OR7.34, 95%CI 2.43-23.06, p = 0.0006), than non-frail patients on univariate analysis(UVA). On multivariable analysis, frailty remained independently associated with grade II-V complications and grade III-V complications (OR4.64, 95%CI 2.31-9.94, p &lt; 0.0001, controlling for stage, operative duration and intraoperative complication, and OR24.49, 95%CI 9.72-70.67, p &lt; 0.0001, adjusting for BMI, stage and operative duration, respectively). On UVA, age, surgical complexity score, and smoking were not predictive of complications. Frailty also independently predicted non-home discharge (OR7.37, 95%CI 2.81-20.46, p &lt; 0.0001) when adjusting for age. Conclusions: Frailty as assessed with mFI-5, independent of age, strongly predicted morbidity and non-home discharge after Gynecologic Oncology surgery. Strategies for perioperative optimization could help address these disparities. mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification.
Passing the Test: A Model-Based Analysis of Safe School-Reopening Strategies
Authors: Alyssa Bilinski, Joshua A. Salomon, John Giardina, Andrea Ciaranello, Meagan C. Fitzpatrick
Journal: Annals of Internal Medicine (2021)

Background: The COVID-19 pandemic has induced historic educational disruptions. In April 2021, about 40% of U.S. public school students were not offered full-time in-person education. Objective: To assess the risk for SARS-CoV-2 transmission in schools. Design: An agent-based network model was developed to simulate transmission in elementary and high school communities, including home, school, and interhousehold interactions. Setting: School structure was parametrized to reflect average U.S. classrooms, with elementary schools of 638 students and high schools of 1451 students. Daily local incidence was varied from 1 to 100 cases per 100 000 persons. Participants: Students, faculty, staff, and adult household members. Intervention: Isolation of symptomatic individuals, quarantine of an infected individual's contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening. Measurements: Transmission was projected among students, staff, and families after a single infection in school and over an 8-week quarter, contingent on local incidence. Results: School transmission varies according to student age and local incidence and is substantially reduced with mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular testing because of the subclinical nature of most children's infections. Teacher vaccination can reduce transmission to staff, and asymptomatic screening improves understanding of local circumstances and reduces transmission. Limitation: Uncertainty exists about the susceptibility and infectiousness of children, and precision is low regarding the effectiveness of specific countermeasures, particularly with new variants. Conclusion: With controlled community transmission and moderate mitigation, elementary schools can open safety, but high schools require more intensive mitigation. Asymptomatic screening can facilitate reopening at higher local incidence while minimizing transmission risk. Primary Funding Source: Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists, National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and Facebook.
Incidence of immune-related adverse events with pembrolizumab in advanced melanoma and correlation with treatment response: A single institution review of irAEs.
Authors: Caitlyn N. Myrdal, Paras Mehta, Eric Smith, Kimberly Briones, Jason Albright, Clara Curiel-Lewandrowski, Ali McBride, Srinath Sundararajan
Journal: Journal of Clinical Oncology (2021)

e21519 Background: Anti-PD-1 therapy has become a mainstay of advanced melanoma treatment. However, associated irAEs are common and contribute to significant delays or cessation of treatment. In this retrospective cohort study, we aim to characterize the real-world irAE profile of pembrolizumab at our institution and its prognostic implications. Methods: We evaluated unresectable stage III-IV melanoma patients treated with pembrolizumab between 2011 and 2016 at the University of Arizona Cancer Center (UACC). Information regarding demographics, treatment, irAEs, and hospitalizations were recorded. Adverse events were graded using the common terminology criteria for adverse events v.4.0 (CTCAE). Results: Seventy-three patients were identified, 4 (5.5%) with unresectable stage III and 69 (94.5%) with stage IV melanoma. The median age was 68; 48 (65.8%) patients were male and 25 (34.2%) were female. Nineteen patients (26.0%) had a preexisting autoimmune disorder. 171 irAEs were identified in 58 of the patients. 141 (82.5%) were Grade 1, 24 (14.0%) were Grade 2, and 6 (3.5%) were Grade 3. Incidence and time to onset of significant events is displayed in Table. Eleven (15%) patients were hospitalized, and 8 patients (11.0%) stopped treatment due to an irAE. Sixteen (84.2%) patients with a preexisting autoimmune condition experienced an irAE versus 78% of patients without an autoimmune condition. Twelve patients (75%) had an exacerbation of their autoimmune condition. Response could be assessed in 67 patients . 30 patients of the 67 (45%) had a CR or a PR and 37 patients (55%) had progressive disease (PD). 58 of 67 (87%) experienced an irAE. 29 (50%) of the 58 irAE patients had PD, while 8 (88.9%) of the 9 non-irAE patients had PD. The relative risk of progression in patients who experienced an irAE versus who did not was 0.56 (95% CI: 0.39-0.79, p= 0.001). Conclusions: Experience with pembrolizumab at our institution suggests a similar irAE profile compared to landmark trials, though we observed a higher percentage of patients who required discontinuation of pembrolizumab (11% versus 5% in Phase III trials). In our retrospective study, the risk for progression was significantly higher in patients without irAE versus with any irAE, suggesting that development of irAE could be a positive prognostic sign.[Table: see text]
Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2
Authors: Anu Goenka, Alice Halliday, Michaela Gregorova, Emily Milodowski, Amy Thomas, Maia Kavanagh Williamson, Holly Baum, Elizabeth Oliver, Anna E. Long, Lea Knezevic, Alistair J.K. Williams, Vito Lampasona, Lorenzo Piemonti, Kapil Gupta, Natalie Di Bartolo, Imre Berger, Ashley M. Toye, Barry Vipond, Peter Muir, Jolanta Bernatoniene, Mick Bailey, Kathleen M. Gillespie, Andrew D. Davidson, Linda Wooldridge, Laura Rivino, Adam Finn
Journal: Cell Reports Medicine (2021)

Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein, with a corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ- and/or TNF-α-producing T cells is comparable between infants and adults. On principal-component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19.
Costs of the immune check point inhibitors versus survival ratio in first-line non-small lung cancer, cost bundling proposal.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2021)

e21034 Background: Pembrolizumab (Pembro) demonstrated marked prolongation of 5-year overall survival (OS) in 1st-line advanced/metastatic (a/m)-non-small lung cancer (nsLC). Adjuvant Durvalumab (Durv), Atezolizumab/Bevacizumab (Atezo/Bev), Ipilimumab/Nivolumab (Ipi/Nivo) and Pembro-combination have since improved the outcome. Progress, however, came at high costs of the immune check point inhibitors (ICI). There is unmet need for cost-constraining policies. We purposed 1- Weigh costs of ICI vs outcome 2- Propose cost bundling at negotiable $450,000 - $550,000 thresholds, depending on the number of companies and drugs involved. Methods: OS, hazard ratio (HR) and survival ratio (SR), defined as (1.0-HR) were used. Chemo-drugs excluded, costs of ICI doses were calculated in US$. Results: Durv one-year costs in unresectable stage III were $130,956, OS gain 363 days and SR 0.47. Pembro one-year costs were $134,778, OS 474 and SR 0.37 in PD-L1 &gt; 50%. At 5 years, costs were $673,890. Bundling negotiated at $450,000-$550,000 would save $123,112-$223,890. Costs of 35 cycles of Pembro-combination were $336,945, OS 339 and SR 0.51. Costs of Atezo/Biosimilar-Bev-comnination supplied by &gt; one company, were $429,744, OS 135 and SR 0.22. Ipi/Nivo costs were $544,696, OS 141 and SR 0.34. Costs of Atezo/Bev and Nivo/Ipi used beyond 2 years exceeded $550,000 and multiplied by one more of use. Costs of Pembro-combination were 0.78 lower than Atezo/Bev and 0.62 than Ipi/Nivo. Pembro SR were 2.32 higher than Atezo/Bev and 1.65 than Ipi/Nivo. Lack of direct comparison undermined Pembro SR advantage. Conclusions: Costs of one-year adjuvant Durv, 3-year Pembro and 35-cycle Pembro-combination seemed equitable with their corresponding SR and below the $450,000 threshold. Pembro-combination costs were cheaper than Atezo/Bev and Nivo/Ipi. ICI costs of extended use tend to support the bundling proposal.
SER-ONCOVID: Seroconversion in solid-tumor cancer patients after COVID-19 diagnosis.
Authors: Anna Pous, Eudald Felip, Olatz Etxaniz, Ainhoa Hernandez Gonzalez, Sofia España, Margarita Romeo, David James Pinato, Anna Esteve, Ricard Mesia
Journal: Journal of Clinical Oncology (2021)

2544 Background: Cancer patients (pts) represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics, COVID-19 and anti-SARS-Cov2 IgG were collected from cancer pts (solid tumors) who tested positive for COVID-19 (PCR+) between March and April 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-Cov2 IgG seroprevalence at 3 and 9 months post infection and explored clinico-pathologic factors associated with IgG positivity. We explored the impact of potential factors influencing antibody production at &gt;9 months. Results: Of 49 pts registered between 10 th March-26 th April 2020, 21 died &lt;3 months after the infection and 5 pts refused to participate, leaving 23 eligible pts for IgG testing. With respect to those not tested, IgG tested cohort was younger (median age: 64.0 vs 72.9 years, p = 0.001) and presented oncologic remission in 68.2% of cases (vs 34.6%, p = 0.043) at COVID-19 diagnosis. Median time from PCR+ to first and second IgG determination was 3.2 months (Interquartile range [IQR]: 2.9-4.1) and 9.5 months (IQR: 8.8-9.8), respectively. Out of 23 pts, 15 had both determinations and 8 had only one (3 in the first time point, 5 in the second one). We identified 16/18 pts IgG+ (88.9%) at 3 months and 17/20 pts IgG+ (85%) at 9 months. One IgG+ pt became IgG- at the second determination, one was IgG- at both timepoints, and one had an inconclusive result at the first but negative at the second timepoint. Key characteristics of patients by IgG result 9 months after COVID-19 diagnosis are shown in the table. Conclusions: We describe a high seroprevalence of anti-SARS-CoV-2 IgG at 3 and 9 months after COVID-19 diagnosis in solid tumour patients, irrespective of anti-cancer therapy exposure. Pts who were IgG+ at 9 months were older, and more likely to have required oxygen during prior COVID-19 in comparison to IgG- pts suggesting that infection severity may promote durable immunity. Frequency of early stage cancers was higher among IgG+ pts, suggesting less cancer-related immunosupression. Older (&gt;70 years) and advanced cancer pts were under-represented in this series, warranting confirmation of these preliminary results in a larger cohort.[Table: see text]