tbuckley/cabot-search huggingface dataset:
Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases
Authors: Selina Tsim, Laura Alexander, Caroline Kelly, Ann Shaw, Samantha Hinsley, Stephen Clark, Matthew Evison, Jayne Holme, Euan J. Cameron, Davand Sharma, Angela Wright, Seamus Grundy, Douglas Grieve, Alina Ionescu, David P. Breen, Elankumaran Paramasivam, Ioannis Psallidas, Dipak Mukherjee, Mahendran Chetty, Giles Cox, Alan Hart-Thomas, Rehan Naseer, John Edwards, Cyrus Daneshvar, Rakesh Panchal, Mohammed Munavvar, Rachel Ostroff, Leigh Alexander, Holly Hall, Matthew Neilson, Crispin Miller, Carol McCormick, Fiona Thomson, Anthony J. Chalmers, Nick A. Maskell, Kevin G. Blyth
Journal: Journal of Thoracic Oncology (2021)

IntroductionMalignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory.MethodsA multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure.ResultsA total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557–0.664], p = 0.0015) and 0.516 [0.443–0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume.ConclusionsSOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.
Prognostic value of early imaging following CAR T-cell therapy in DLBCL.
Authors: Amneet Bajwa, Ying Huang, Rui Li, Nathan Denlinger, Jonathan Edward Brammer, Ayman A. Saad, Samantha Jaglowski, Adam Kittai
Journal: Journal of Clinical Oncology (2021)

e19559 Background: Chimeric antigen receptor T-cell (CART) therapies lead to durable disease control in patients (pts) with relapsed/refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL). We assessed the prognostic value of response on first staging scan, and whether pts with progression of disease (PD) convert to a response on second scan. Methods: We conducted a retrospective analysis of pts with R/R DLBCL treated with CART at our institute. Baseline characteristics were assessed at apheresis. We included staging scans (CT, PET-CT and MRI) that occurred up to 6 months (mos) after CART infusion. Responses were determined via the Lugano 2014 criteria. Overall survival (OS) was calculated from first scan to last follow-up. Kaplan Meier method and Cox model were used to correlate first scan result with OS. Results: Of the 118 pts who received CART, 111 pts had evaluable staging scans (7 passed prior to first scan). Of the 111 pts, median age was 61 years (range, 23-84), and median number of prior therapies was 3 (range, 1-7). 61 pts received tisagenlecleucel, and 50 pts received axicabtagene ciloleucel. 22% of pts had MYC rearrangement by FISH. The majority of pts were stage 3/4 (91%), with an IPI score ≥2 (82%). 32%, 66% and 2% of pts had a CT, PET-CT or MRI as their first scan respectively. After a median follow-up of 16.2 mos, median OS from first scan was not reached (NR) (95% CI, 17-NR). 37%, 5%, 32%, 25% of pts had PD, SD, PR, and CR on first scan respectively. Median time to first scan was 59 days (range, 13-115). Median OS for pts who had PD was 3 mos (95% CI 2-8), and the median OS for those who attained SD, PR or CR was NR (95% CI NR-NR). Accounting for statistically important factors on multivariate analysis, PD on first scan was an independent predictor of OS (p&lt;.001, HR 10.1 (95% CI 4.7-22)). We observed no evidence that pts with PD on first scan convert to a response on second scan without intervention. 26 of 41 pts who had PD did not start new treatment, 17 passed without follow-up scan, 1 is in follow-up, and 8 continued to show PD on subsequent scans. Conclusions: PD on first staging scan is a strong prognostic marker for survival for pts with R/R DLBCL who receive CART. There is no evidence to suggest conversion to a response will occur for patients who have PD. Performing staging scans at an earlier time-point has value, allowing for earlier treatment changes and goals of care conversations in this pt population.[Table: see text]
Immune-related adverse events associated with immune-checkpoint inhibitors therapy in Mexican patients: Experience at a single center.
Authors: Iván Romarico Romarico Gonzalez Espinoza, Neil Cortés Escobar, Mariana Chiquillo-Domínguez, Gabriela Juárez Salazar, Julio Cesar Garibay Diaz, Anna Gozalishvili Boncheva, Eric Acosta Ponce De León, Sergio Sánchez Sosa, Rebeca Ibarra Fernández, Enrique Miguel Cruz, Mónica Sabaté Fernández, Juan Carlos García Reyna, José Manuel Aguilar Priego, Alfredo Domínguez Peregrina, Giovanni Tobón Helú, Carlos Cordero Vargas, María de Jesús Gonzalez Blanco, Carmen Aguilar, José Carlos Arroyo Kuribreña, Feliciano de Jesús Vizcarra Ramos
Journal: Journal of Clinical Oncology (2021)

e14580 Background: The use of immune-checkpoint inhibitors (ICIs) for solid malignancies is rapidly rising, and many new agents and treatment combinations are in development. However, ICIs have a unique side-effect profile of immune-related adverse events (irAEs) compared with chemotherapeutic agents or targeted therapies. The aim of this work was to describe the irAEs in diverse types of malignant tumors using real-world data. Methods: This is a retrospective and descriptive study of patients with diverse types of advanced malignancies treated with immunotherapy at Centro Oncológico Integral of the Hospital Ángeles in Puebla, México; during the period 2016-2020. Data about the primary neoplasm, ICIs, irAEs, organ system affected, grade and treatment was collected. Clinical and laboratory parameters were obtained by reviewing medical records. Results: A total of 117 patients were included, median age of 65 years, of which 63.2% were male and 36.8% were female. The most frequent neoplasms treated with ICIs were: lung (27.4%), kidney (16.2%), melanoma (12.8%), hepatocellular (9.4%), breast (8.5%), non-melanoma skin cancer (6.0%), mesothelioma (4.3%) and other tumors (15.3%). 39.3% of the patients had no metastases, 41.9% had metastases to at least 1 or 2 sites, and 18.8% to 3 or more sites. The types of ICIs were: nivolumab (35.0%), pembrolizumab (28.2%), atezolizumab (23.9%), ipilimumab + nivolumab (12.0%) and durvalumab (0.9%). The most frequent irAEs were: gastrointestinal (61.5%), neurologic (46.2%), pulmonary (38.5%), metabolic (32.5%) and hematologic (29.1%). 39.3% of the irAEs were reported as grade 1, 31.6% as grade 2, 14.5% as grade 3 and 2.6% as grade 4. Conclusions: Our work shows the incidence of irAEs in a poorly studied population and provides new data that complement that reported by other works, however, further prospective studies are necessary.[Table: see text]
Association of chronic use of proton pump inhibitors with an increased risk of immune checkpoint inhibitor-induced colitis in renal cell carcinoma.
Authors: Roy Elias, Jianyi Yin, Lan Peng, Alana Christie, Nisa Kubiliun, James Brugarolas, Hans J. Hammers
Journal: Journal of Clinical Oncology (2021)

e16550 Background: Immune checkpoint inhibitors (ICI) have become standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including immune-related colitis (irC). Growing evidence suggests that proton pump inhibitors (PPIs) are associated with an increased risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and irC, we sought to evaluate the relationship between PPI use and irC in mRCC patients. Methods: We performed a retrospective study of adult patients who received ICI for mRCC between 2015 and 2018 at two tertiary care centers. Clinical characteristics, oncological outcomes, irC details, and PPI use were collected by manual chart review. The diagnosis of irC was made via biopsy when available, or when unavailable (or inconclusive) by clinical criteria. Univariable and multivariable logistic regression analyses were conducted to assess PPI use and other potential risk factors of irC. Results: A total of 176 patients received immunotherapy for mRCC, of which 16 (9.1%) were diagnosed with irC. There were no significant differences between patients with and without irC in age, gender, medical comorbidities, RCC subtype, treatment history, and overall survival. However, Caucasian race, exposure to ipilimumab, and PPI use were more frequently observed in patients with irC than those without. Patients with irC presented with elevated stool lactoferrin and calprotectin and a wide range of endoscopic and histologic findings. In univariable and multivariable logistic regression analyses, Caucasian race, exposure to ipilimumab and chronic use of PPIs &gt;8 weeks were significantly associated with irC (Table). Conclusions: PPI use may be a modifiable risk factor for irC development in patients with mRCC.[Table: see text]
Characteristics of patients hospitalized through the emergency department with an oncology drug-related side effect.
Authors: Elisea Avalos-Reyes, Darren Parke, Kirsten Wallace, Allison Freeman, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2021)

6557 Background: Recent advances in oncology treatment present an expanding spectrum of cancer-treatment-related emergencies. Many aspects of healthcare utilization, specifically emergency department (ED) visits, are not well studied in this population. The purpose of this study is to determine (1) what proportion of cancer patients visit the ED with an oncology drug-related side effect and are admitted and (2) what factors impact the probability of inpatient admission among these patients. Methods: This study evaluated ED visits by adult patients undergoing active drug treatment for cancer insured by a large commercial and Medicare health plan in the United States between January 1, 2018, and September 30, 2019. Among cancer-related ED visits, logistic regression was used to determine the marginal effect of demographic and clinical characteristics of patients on acute inpatient admission. Results: There were 39,921 total ED visits among patients undergoing drug treatment for cancer; of these, 76% presented with an oncology drug-related side-effect. 36% of all ED visits resulted in admission, 5% resulted in an observation stay. After adjusting, age was not a significant predictor of inpatient admission. Being male (p &lt; 0.01) and living in urban (p &lt; 0.01) or suburban (p &lt; 0.01) zip codes significantly increased the likelihood of admission. Patients with colorectal (p = 0.019), gastrointestinal (p &lt; 0.01), blood (p &lt; 0.01), lung (p &lt; 0.01), metastatic (p &lt; 0.01) cancers, or Hodgkin’s lymphoma (p &lt; 0.01) had significantly increased risk of admission. Patients with prostate (p &lt; 0.01) cancer had a significantly reduced risk of admission. The primary complaint upon presentation to the ED was the most important predictor of inpatient admission; sepsis, pneumonia, medical complications, white cell disorders, metastatic cancer, and fractures were all associated with a significantly higher (all p &lt; 0.001) risk of admission. Patients with comorbid heart failure (p &lt; 0.001), those taking ulcer medications (p &lt; 0.01), or inflammatory bowel disease (p = 0.03) had a significantly increased risk of admission. Results were consistent regardless of payer (Medicare or commercial health plan). Conclusions: This study identified cancer patients for whom acute inpatient admission from an ED presentation is more likely. Future studies identifying cancer patients who may be at risk of making an ED presentation based on demographic, clinical and disease-related characteristics are needed and may help inform targeted follow up of patients to mitigate potentially avoidable ED presentation and subsequent inpatient admission.
Acceleration of blood-based circulating cell-free DNA epigenetic age among HIV-infected patients with hepatocellular carcinoma in Nigeria.
Authors: Yinan Zheng, Claudia Hawkins, Edith Okeke, Olufunmi A. Lesi, Yishu Qu, Lewis R. Roberts, Demirkan Gursel, Fatimah Biade Abdulkareem, Alani Akanmu, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwnag-Youn Kim, Wasiu Lanre Adeyemo, Firas Hazem Wehbe, Chad Achenbach, Atiene Sagay, Folasade Ogunsola, Robert Murphy, Lifang Hou
Journal: Journal of Clinical Oncology (2021)

e16137 Background: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality in Nigeria. HIV and viral hepatitis B (HBV) and C (HCV) co-infection are common in Nigeria that significantly accelerates liver disease progression including HCC. Aging-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HIV-associated HCC. We examined the epigenetic age acceleration (EpiAgeAccel) in ccfDNA in HCC patients with HIV. Methods: The study included three groups of participants: a) HIV positive with HCC (n=7); b) HIV positive and cancer-free (n=45); and c) HIV negative with HCC (n=33). Epigenetic age was estimated by Horvath’s calculator using genome-wide ccfDNA methylation data profiled by Illumina EPIC array. EpiAgeAccel was computed as the residuals of a linear model of epigenetic age on chronological age, namely the unexplained portion of epigenetic age by chronological age. We used multiple linear regression to compare EpiAgeAccel between HIV/HCC groups, adjusting for sex, age, education, alcohol intake, and HBV/HCV infection. Results: Among HIV positive participants, there was a higher percentage of men (57% vs. 22%, p&lt;0.001), HBV infection (29% vs. 11%, p=0.004), and HCV infection (57% vs. 2%, p&lt;0.001) in the HCC group compared to the cancer-free group. EpiAgeAccel was 4.8 years higher in HIV positive patients with HCC compared to cancer-free HIV positives (p=0.02). Among HCC patients, EpiAgeAccel was 2.1 years higher in HIV positives compared to HIV negative but not statistically significant. Conclusions: Epigenetic age in ccfDNA is accelerated in HIV-positive HCC patients. EpiAgeAccel measured in ccfDNA may be developed into a surrogate biomarker for minimally invasive HCC detection among HIV-infected patients in low- and middle-income countries.
A methodology for the extraction and analysis of real-world radiographic and electronic medical record data to reconstruct treatment arms of historical prostate cancer clinical trials.
Authors: William David Lindsay, Christopher A. Ahern, Aaron Kamauu, Robert Wilder, Karen Chagin, Timmothy Taps
Journal: Journal of Clinical Oncology (2021)

5033 Background: Real-world evidence (RWE), including synthetic comparator arms created from historical real-world data (RWD), has the potential to support the safety and efficacy evaluation of new medical products. However, many available RWD sources lack the details necessary to reliably identify patients comparable to clinical trial cohorts or to assess essential oncologic efficacy endpoints. This project demonstrates the ability to extract and analyze RWD to identify patients matching eligibility criteria to four historical clinical trials in metastatic castration-resistant prostate cancer (mCRPC), and calculate outcome measures. Methods: A total of 5,741 patients treated for prostate cancer at multiple institutions (2010-2020) were analyzed in two cohorts using data extracted from the EMR, Tumor Registry, Oncology Information System, and Picture Archiving and Communication System. Of 3,486 patients with prostate cancer in Cohort 1, 422 mCRPC patients were identified: those treated with ADT who achieved castration-level testosterone ( &lt; 50 ng/dL), had evidence of metastatic disease, and exhibited rising PSA (PCWG2). These patients were further matched to four historical clinical trial treatment arms (COU-AA-301: 49, COU-AA-302: 143, AFFIRM: 30, PREVAIL: 79), based on prior chemotherapy and receipt of Abiraterone or Enzalutamide. Overall survival (OS) and time to skeletal related events (SRE) (pathological fracture, spinal compression, surgery to bone, and radiotherapy to bone) were calculated based on diagnosis and procedure codes using the Kaplan-Meier (KM) Estimator. Of 2,255 patients with prostate cancer in Cohort 2, 101 patients received Abiraterone or Enzalutamide and 59 patients had sufficient baseline and follow-up imaging to be scored. Radiographic progression-free survival (rPFS) was calculated from the start of treatment to the time of progression (RECIST 1.1) or loss to follow-up using the KM estimator. Results: In Cohort 1, median OS was 37.7 months (95% CI: 31.5-NR), and median time to SRE was 17.9 months (13.5-22.6). Median OS per patient cohort matched to historical trial treatment arm was COU-AA-301: 23.7 months (10.7-NR), COU-AA-302: 45.9 months (34.9-NR), AFFIRM: 35.3 months (6.34-NR), PREVAIL: 41.5 months (21.9-NR). In Cohort 2, median rPFS was 37.2 months (13.3-NR). Conclusions: The methodology employed in this analysis not only successfully identified a cohort of RWD patients similar to clinical trial-defined patients, but also curated sufficiently reliable data to calculate essential endpoints (e.g., rPFS). At scale, this methodology can be used to generate RWE, including synthetic comparator arms to support clinical trials with radiographic endpoints.
Vaccination coverage in cancer outpatients: An interventional multicenter before/after study.
Authors: Pierre Rivière, Nicolas Penel, Karine Faure, Guillaume Marie, Sophie Panaget
Journal: Journal of Clinical Oncology (2021)

e24026 Background: Despite largely diffused guidelines, Pneumococcal and Influenza vaccination coverage (VC) remains insufficient in cancer patients receiving chemotherapy. We evaluated VC and carried out an interventional study to improve VC in cancer patients treated in 3 medical oncology departments in 3 hospitals of North-of-France. Methods: Using a standardized questionnaire, we assessed the VC in adult cancer patients receiving anticancer treatment in day hospital between 02 and 07 Dec. 2019. Then, in each hospital, we organized trainings with physicians to discuss the current vaccination guidelines (January 2020). Finally, to assess the impact of this intervention on Pneumococcal and Influenza VC, we have conducted a similar survey using the same questionnaire in March 2020. Since there were no specific guidelines on Diphtheria-Tetanus-Pertussis (DTP) VC and we did not expect an improvement, we have monitored DTP VC as internal control. Results: 272 patients have been enrolled in the “before study” in the 3 hospitals, whereas 156 patients have been enrolled in the “after study” in only 2 hospitals (the after-study was not feasible in 3 rd hospital because of COVID-19 pandemic national containment). Predictors associated with DTP VC was age, with Pneumococcal VC was center and with Influenza VC were age, gender and tumor histology (adenocarcinoma vs others). Influenza VC was significantly improved after intervention (42.6 vs 55.1% with p = 0.016) especially in fragile patients, but Pneumococcal VC was not (11.8 vs 15.4% with p = 0.357). Conclusions: As expected, VC was very low in cancer patients, our figures are consistent with literature data. The impact of intervention (training of physicians) is limited without improvement of Pneumococcal VC. We presume that this increase in Influenza VC mainly reflects the overall result of national Influenza vaccination campaign.
Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG)*
Authors: E. A. Olsen, M. Harries, A. Tosti, W. Bergfeld, U. Blume‐Peytavi, V. Callender, V. Chasapi, O. Correia, G. Cotsarelis, R. Dhurat, N. Dlova, I. Doche, N. Enechukwu, R. Grimalt, S. Itami, M. Hordinsky, K. Khobzei, W. ‐S. Lee, S. Malakar, A. Messenger, A. McMichael, P. Mirmirani, Y. Ovcharenko, S. Papanikou, G. M. Pinto, B. M. Piraccini, R. Pirmez, P. Reygagne, J. Roberts, L. Rudnicka, D. Saceda‐Corralo, J. Shapiro, T. Silyuk, R. Sinclair, R. O. Soares, A. Souissi, A. Vogt, K. Washenik, A. Zlotogorski, D. Canfield, S. Vano‐Galvan
Journal: British Journal of Dermatology (2021)

Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. To enable data to be collected worldwide on FFA using common criteria and assessment methods. A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.