tbuckley/cabot-search huggingface dataset:
Proton pump inhibitors and antibiotics impact on toxicities and clinical outcomes in cancer patients treated with immunotherapy.
Authors: Haniel alves Araujo, Camila Motta Venchiarutti Moniz, Oddone Freitas Melro Braghiroli, Milena Perez Mak, Lucas Fernando Uratani, Ricardo Dahmer Tiecher, Priscila Muniz Moraes, Ingrid Barbosa, Veridiana Pires De Camargo, Maria Ignez Freitas Melro Braghiroli, Gilberto Castro, Paulo Marcelo Hoff, Maria Del Pilar Diz
Journal: Journal of Clinical Oncology (2021)

2652 Background: Gut microbiome dysbiosis impairs systemic immune responses and recent evidence suggests its critical role in patients (pts) treated with immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) and antibiotics (ATB) may alter the microbiome and their impact on clinical outcomes and toxicities requires further investigation. Methods: This retrospective cohort included consecutive metastatic cancer pts treated with ICI with palliative intent. We reviewed pts' records, concomitant medication and toxicities graded by CTCAE 4.0. Pts with PPI or ATB exposure were analyzed according to previous use (pPPI and pATB, ≤60 days to ICI) and concomitant use (cPPI and cATB). We estimated median overall survival (mOS) and progression free survival (PFS) by Kaplan–Meier and used a Cox proportional-hazards model to adjust for differences in baseline characteristics. Toxicities and ATB/PPI interaction was calculated using Pearson Chi-square method. Results: We enrolled 216 pts with a median age of 59 years, mostly ECOG-PS 0 (34%) or 1 (58%). ICI employed were mostly anti-PD-1 (60.2%), anti-CTLA-4 (16.2%) and anti-PD-L1 (12.5%). Most frequent primary tumor sites were lung n = 39 (18.1%), gastrointestinal n = 34 (15.7%) and melanoma n = 33 (15.2%). Half of the pts (108) received ATB and 114 (52.8%) PPI. Compared to control, pPPI group n = 57 (26.4%) had shorter mOS (11.6m vs 19.7m, p &lt; 0.001) and PFS (2.8m vs 8.5m, p &lt; 0.001), but no statistically significant difference in toxicities grade ≥3 and/or leading to ICI discontinuation (36% vs 29.1%; p = 0.29). cPPI n = 100 (46.3%) depicted a negative impact on mOS (12.1m vs 17.0m; p = 0.01), PFS (4.3m vs 7.1m; p = 0.04) and augmented toxicities (42% vs 19%; p &lt; 0.001). pATB n = 34 (15.7%) had shorter OS (6.9m vs 19.3m, p &lt; 0.001) and PFS (3.2 vs 7.2m, p = 0.005) and higher incidence of toxicities (45.9% vs 28.1%; p = 0.04 ). cATB use n = 92 (42.6%) did not impact OS (12.1m vs 15.6m; p = 0.32) or PFS (5.5m vs 5.9m; p = 0.82), but had a higher incidence of toxicities: 37% vs. 24.2% (p = 0.05). Multivariate analyses confirmed that pATB therapy and pPPI respectively remained as independent prognostic variables associated with OS (HR 2.39; 95% CI, 1.60-3.59; P &lt;.001 and HR 1.73; 95% CI 1.23-2.44; P = 0.002) and PFS (HR 1.72; 95% CI, 1.14-2.61; P = 0.01 and HR 2.36; 95% CI 1.67 - 3.34; P &lt; 0.001) adjusted by performance status, age and line of treatment. Conclusions: These data suggest that concomitant use of PPI and ATB is associated with increased toxicities in ICI treated pts. pPPI and pATB can negatively impact OS and PFS and merit clinician’s attention.
Phase III randomized clinical trials global distribution and funding: Trends and disparities.
Authors: Karina Pinheiro, Mauricio Ribeiro, Luiza Lara Gadotti, Fabiane Marson, Carlos Diego Holanda Lopes, Rodrigo Saddi, Joao Victor Machado Alessi, Artur Katz
Journal: Journal of Clinical Oncology (2021)

e18563 Background: Phase III clinical trials (PIIICT) constitute the cornerstone of the progress and development of new therapeutic strategies. However, their complexity and costs in a scenario of limited funding sources impose important limitations in their scope and reach. Methods: We searched in clinicaltrials.gov to identify PIIICT evaluating pharmacological interventions in adjuvant, neoadjuvant and metastatic settings between 2010-2020 in breast, cervix, colorectal cancer (CRC), lung, melanoma, prostate and penile cancer. Trials identified were categorized according to disease site, funding source and world region/country (R/C). Case incidence in 2020 was collected from the IARC website. Results: Of 825 clinical trials, 72.7% were industry-sponsored (IS). Trials by R/C, not including multicentric studies (61.8%): (A) USA 76 trials, 53.9% non-industry sponsored (NIS); (B) Europe/UK 112, 59.8% NIS; (C) Asia (excluding China) 62, 27.4% NIS and (D) China 183, 43.7% NIS. There was a statistically significant association between location and funding source (p= 0.0003). NIS source was detected in higher proportion of trials ongoing in regions A and B (59%). IS was statistically less frequent in uterine cervix/penis (42.8%) and CRC (49.6%) IS was significantly higher in lung and prostate trials (both 81%) (p&lt;0.0001). Table summarizes our results by tumor sites. We also found a statistically significant association between the incidence of malignancies in the selected primary sites and the amount of registered clinical trials, overall (p&lt;0.0001) and IS as well (p&lt;0.0001). The database is under expansion to include other disease sites as well as other geographic areas separately (Africa, Russia, South America, India, and Oceania). Cervix and penile results were combined given their biological and epidemiological similarities. Conclusions: There is a significant disparity between the number of clinical trials and tumor prevalences as well as among the distribution of IS trials funding.[Table: see text]
A prognostic model based on CGGA and TCGA databases for predicting outcome of glioma patients.
Authors: Hongbin Ni, Xing Zhang, Xiaoxuan Wang, Chao Song
Journal: Journal of Clinical Oncology (2021)

e14017 Background: Glioma is the most frequent primary malignance of the central nervous system (CNS) and causes the top-ten deaths of cancers. Isocitrate dehydrogenase ( IDH) mutations and chromosome 1p and 19q codeletion are the known prognostic factors of glioma. However, it is still not enough to predict the outcomes. Herein, we conduct a prognostic model of patients with gliomas. Methods: The Chinese Glioma Genome Atlas (CGGA) contained 286 patients with whole-exome sequencing (WES) was used to established the model. Kaplan-Meier analysis based on log-rank test was used to confirm the single mutation overall survival (OS) factors (allele frequency≥ 5) in CGGA. The model was established based on the Cox regression of above significant factors. The data of 1122 patients with glioma in TCGA (The Cancer Genome Atlas) was used to validate the model. Results: According to the CGGA database, the OS factors of glioma patients were 1p/19q, CIC, EGFR ( p&lt; 0.001), IDH1, IRS2, NF1, NOTCH1, PDGFRA, PTEN, ROS1, SMARCA4 and TP53. The Cox regression revealed 1p/19q codeletion (HR = 2.008, 95%CI 1.397-2.885, p&lt; 0.001), EGFR (HR = 0.420, 95%CI 0.217-0.811, p= 0.010), PDGFRA (HR = 0.271, 95%CI 0.139-0.528, p&lt; 0.001), and ROS1 (HR = 0.197, 95%CI 0.071-0.549, p= 0.002). Based on the β value of the regression equation, we divided the glioma patients into 3 groups (G1: harboring EGFR, PDGFR and/or ROS1 mutations; G2: wide type; G3: harboring 1p/19q without mutations in three genes). In TCGA, the OS of glioma patients was also showed G1 &lt; G2 &lt; G3 significantly. Conclusions: The prognostic model was divided glioma patients into three groups reasonably and could provide new reference for the glioma management. It needed to be further verified in more cohorts.
Barriers to web-based symptom management systems (web-SyMS).
Authors: Michael J. Hassett, Angela Tramontano, Christine Cronin, Raymond U. Osarogiagbon, Sandra L. Wong, Jessica J Bian, Hannah W. Hazard, Don S. Dizon, Deborah Schrag
Journal: Journal of Clinical Oncology (2021)

6545 Background: Web-SyMS can reduce the burdens of cancer and its treatment. While patients frequently express willingness to use these systems, only a subset actively engages with them. Some patients may lack the tools and confidence needed to benefit from web-SyMS. We sought to characterize these barriers among community-based cancer patients receiving care across six diverse healthcare systems. Methods: We surveyed patients receiving chemotherapy at three healthcare systems (Baptist, TN; Maine Medical, ME; Dana-Farber, MA) and patients recovering from cancer-directed surgery at three healthcare systems (West Virginia University, WV; Dartmouth-Hitchcock, NH; Lifespan, RI). Surveys were conducted as part of a pre-implementation analysis of eSyM – an EHR-embedded web-SyMS that collects, tracks, and manages patient reported outcomes during cancer therapy. Results: Among 563 respondents, access to tech devices (i.e., tablet, computer, or smartphone) was high: 78% reported access to ≥2 devices and only 5% reported access to no devices. However, confidence using tech devices to accomplish online tasks varied: 45% very confident, 38% somewhat confident, 11% little-no confidence. Compared to medical oncology patients, surgery patients were more likely to report being very confident (57% vs. 31%). There were significant differences based on patients’ self-reported tech confidence (Chi-square P&lt;.05 for all values in the table). Conclusions: Low self-reported tech confidence may identify patients who are at high risk for experiencing the burdens of cancer but may be less likely to benefit from web-SyMS. Addressing this barrier is critical to improving outcomes and addressing disparities. Clinical trial information: NCT03850912. [Table: see text]
Trends in female representation in clinical practice guidelines (CPGs) among major cancer organizations.
Authors: Madhuri Chengappa, Ronald S. Go, Thejaswi K. Poonacha
Journal: Journal of Clinical Oncology (2021)

11006 Background: While women representation and sex disparities in National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) has been studied in a limited set of CPGs, the sex representation and disparity trend over time among all NCCN and ESMO CPG panelists has not been studied. Our study evaluates the current sex disparities and female representation for all NCCN and ESMO CPGs as of 2020 and compared it to the 2010 CPGs of both organizations. Methods: The 2010 and 2020 version of NCCN and ESMO CPGs were examined from their respective websites and archives. We catalogued the number of female versus male panelist for each CPG. We discerned the sex of the panelists based on google search and the panelists’ affiliated institutional websites. Results: 60 NCCN (2020), 51 NCCN (2010), 78 ESMO (2020) and 55 ESMO (2010) CPGs inclusive of all cancers by site, detection prevention and risk reduction, supportive care, and guidelines for specific population were reviewed. NCCN 2020 CPGs had 55.5% female representation. 35 (58%) NCCN CPGs had predominant female representation (&gt;50% of the members being female) whereas 24 CPG (40%) were male predominant (&gt;50% of the members being male). Solid tumors had 24 CPGs with male predominance and hematological malignancies had 14 CPGs with female predominance. Cancers specific to women had higher proportion of female panelist. NCCN 2010 CPGs had 27.1% female representation. Both solid tumors and hematological malignancies had male predominance (82% and 75% respectively). Breast cancer screening, palliative care and older adult oncology CPGs were female predominant. ESMO 2020 had 27.8% female representation. Both solid tumors (37 CPGs) and hematological malignancies (17 CPGs) had predominant male representation (72% and 85% respectively). Breast and ovarian cancer CPGs were female predominant. ESMO 2010 had 23.2% female representation. Male representation was predominant in both solid tumors (35 CPGs) and hematological malignancies (9 CPGs). Breast, cervical and ovarian cancer CPGs were female predominant. Conclusions: Over the last decade, proportion of female panelists in NCCN CPGs has doubled with more than 50% representation among its 60 CPGs, indicating adequate representation of women. In ESMO, although there has been a significant improvement in female representation in hematological malignancies over time, it continues to have overall female underrepresentation (&lt;30%).[Table: see text]
OMIC-06. MOLECULAR SUBGROUPING OF MEDULLOBLASTOMA VIA LOW-DEPTH WHOLE GENOME BISULFITE SEQUENCING
Authors: Dean Thompson, Jemma Castle, Debbie Hicks, Steve Clifford, Ed Schwalbe
Journal: Neuro-Oncology (2021)

Abstract Introduction International consensus recognises four molecular subgroups of medulloblastoma, each with distinct molecular features and clinical outcomes. The current gold-standard for subgroup assignment is DNA methylation microarray. There is an unmet need to develop platform-independent subgrouping assays which are both non-proprietary and compatible with rapidly-expanding WGS capacity in healthcare. Whole Genome Bisulfite Sequencing (WGBS) enables the assessment of genome-wide methylation status at single-base resolution. Previously, WGBS adoption has been limited by cost and sample quality/quantity requirements. Its application for routine detection of medulloblastoma subgroups has not previously been reported. Methodology Two datasets were utilised; 36 newly-sequenced low-depth (10x coverage) and 34 publicly-available high-depth (30x) WGBS medulloblastomas, all with matched DNA methylation microarray data. We compared platform concordance and identified molecular subgroups. Machine-learning WGBS-based subgroup classifiers were optimised and compared between platforms. Aneuploidy and mutation detection using WGBS was optimised and compared to microarray-derived estimates where possible. Finally, comprehensive subgroup-specific DNA methylation signatures were identified. Results We optimised a pipeline for processing, quality control and analysis of low-depth WGBS data, suitable for routine molecular subgrouping and aneuploidy assessment. We demonstrated the suitability of fresh-frozen and FFPE DNA for WGBS, and, using downsampling, showed that subgroup calling is robust at coverages as low as 2x. We identified differentially methylated regions that, due to poor representation, could not be detected using methylation microarrays. Molecular subgroups of medulloblastoma assigned using WGBS were concordant with array-based definitions, and WGBS-derived classifier performance measures exceeded microarray-derived classifiers. Conclusion We describe a platform-independent assay for molecular subgrouping of medulloblastoma using WGBS. It performs equivalently to current array-based methods at comparable cost ($405 vs $596) and provides a proof-of-concept for its routine clinical adoption using standard WGS technology. Finally, the full methylome enabled elucidation of additional biological heterogeneity that has hitherto been inaccessible.
A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.
Authors: Greg Andrew Durm, Muhammad Furqan, Lawrence Eric Feldman, Malini Patel, Richard Delmar Hall, Shadia Ibrahim Jalal, Thomas J. Birdas, Kenneth Kesler, Karen Marie Rieger, DuyKhanh Ceppa, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2021)

TPS8583 Background: There are approximately 35,000 cases of stage I lung cancer in the United States each year. While these patients have better 5-year overall survival (OS) rates than their counterparts with locally advanced and metastatic disease, there is still considerable room for improvement. Based on a recent publication validating the 8 th edition of the TNM classification, the 5-year OS for node-negative pathologically-staged NSCLC between 1-4cm ranges from 73-86%, and recurrence rates for resected stage I NSCLC can range from 18-38%. Previous studies looking at adjuvant chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 ≥50% vs. &lt; 50% and tumor size of 1-2cm vs. &gt; 2-4cm. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is disease free survival (DFS), and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 6 patients enrolled. Clinical trial information: NCT04317534.
COVID-19 outcomes in patients with a history of breast cancer: A diverse multicenter Los Angeles cohort study.
Authors: Nikhita Kathuria-Prakash, Lauren Antrim, Alexander W Sun, Irene Kang, Maria De Lourdes Garcia-Jimenez, Trevor E Angell, Melissa G Lechner, Gino Kim In
Journal: Journal of Clinical Oncology (2021)

e12544 Background: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has affected over 100 million individuals during the current pandemic. Cancer is a reported risk factor for worse outcomes from SARS-CoV-2 infection and its clinical syndrome COVID-19. However, risk associated with specific cancer subtypes, extent of disease, and treatment history remains unclear. Breast cancer is the most common cancer in women and is treated with multiple modalities that may affect COVID-19 severity and outcomes, including surgery, radiation (RT), hormone therapy (HT), and chemotherapy (CT). Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 and history of breast cancer at two academic centers in Los Angeles, CA between January – September, 2020. Demographic information, cancer diagnosis, treatment history, comorbid conditions, and clinical outcomes of COVID-19 were reviewed. The primary outcome was rate of hospitalization for COVID-19. Associations were evaluated for significance by chi-square test or Student’s T test, with a = 0.05. Results: Our cohort included 61 patients with history of breast cancer. 19 (31.1%) required hospitalization and 3 (4.9%) died from COVID-19. Median age was 61 years. 44% of patients were White/Caucasian, 37.7% Hispanic/Latinx, 8% Black/African American, 5% Asian, and 5% were of another race. 87% of patients had local or regional disease and 13% had distant metastases. 53% of patients had ever received CT historically, 66% HT, and 53% RT. 25% of patients received cancer treatment (surgery, CT, or RT) within 90 days of COVID-19 diagnosis. 38% were on HT at time of COVID-19 diagnosis. Patients with prior RT were more likely to be hospitalized from COVID-19 than those with no prior RT (44% vs 14%, p = 0.02), as were patients with 2 or more comorbidities (p = 0.01). In addition, there was a trend toward lower hospitalization rates for patients on HT [24% vs. 42% (p = 0.17)] and a trend toward higher hospitalization rate for non-white ethnicity [35% vs. 25% (p = ns)]. Extent of disease, history of CT, or receipt of any cancer treatment (e.g. surgery, RT, CT) within 90 days of COVID-19 diagnosis were not associated with hospitalization rate. Conclusions: In our diverse cohort of breast cancer patients with COVID-19 a history of RT and presence of multiple comorbidities were both associated with increased risk of hospitalization, while a history of HT was not. Further investigation is needed to validate these findings in larger cohorts. These findings may inform recommendations for breast cancer patients during the ongoing SARS-CoV-2 pandemic.
High intensity interval training safety and efficacy in patients with advanced NSCLC receiving systemic treatment: Results of a prospective trial.
Authors: Myriam Nait Ajjou, Guillaume Bastarache, Emily Walsh, Bertrand Routy, Normand Blais, Mustapha Tehfe, Genevieve Coulombe, Raafat Alameddine, Marie Florescu
Journal: Journal of Clinical Oncology (2021)

12054 Background: Patients with advanced NSCLC experience fatigue and physical deconditioning altering their quality of life. Safety and feasibility of high intensity exercise in advanced NSCLC has not been explored yet. Methods: We report the results of a single-center, prospective two-arm study. Patients with advanced NSCLC actively receiving systemic therapy or having completed treatment less than 2 months prior to enrollment were included. Patients were allocated to either an intervention arm consisting of kinesiologist supervised high intensity interval training (HIIT) at 2 sessions per week for a total of 12 weeks; or a control arm of home exercise guided by an informative pamphlet. All patients were evaluated at baseline, 6 and 12 weeks by a kinesiologist. Quality of life (QoL) exercise surveys and measurement of strength were measured. Results: Sixty patients were enrolled between January 2018 and March 2020. The study was interrupted due to COVID-19. Thirty-two patients were included in the exercise program and 28 patients in the control group. Both groups were balanced in respect to baseline characteristics. A total of 32 (53%) patients went off protocol, 13 (18%) patients stopped due to symptomatic disease progression which included 2 (3%) deaths, 2 (3%) stopped due to COVID-19 preoccupations and the remaining patients withdrew for other reasons. 42 (70%) patients were evaluated at 6-weeks and 28 (47%) completed the 12-week follow-up, with equal distribution in each group. There were no significant difference at 12 weeks in the physical assessment nor the overall QoL scores between both groups: FACT-L on 135 points (+4.1 vs +1.7, p = 0.342) and FACIT on 52 points (+3 vs -0.2, p = 0.832). Patients in the exercise group demonstrated a significant improvement at 12 weeks in the Lung Cancer Symptoms domain on 28 points (22.3 vs 19.8, p = 0.015) as well as the Physical Wellbeing domain on 28 points (23.6 vs 20.6, p = 0.056) compared to the control group, respectively. No significant exercise related complications were reported. After the study, 9 of the 14 patients (64%) who completed the HIIT program continued to exercise virtually with a kinesiologist in contrast to none in the control group. Conclusions: This study demonstrated the safety and potential benefit of a HIIT program on lung-specific and physical wellbeing in patients with advanced NSCLC on active treatment. This study provides further support on the role of supervised physical exercise in patients living with cancer. Clinical trial information: 16.229.