tbuckley/cabot-search huggingface dataset:
Factors associated with cancer screening adherence amongst Latinos in Indiana: Results of an electronic survey.
Authors: Manuel Ricardo Espinoza Gutarra, Susan M Rawl, Robin E. Valenzuela, Erik Parker, Lilian Golzarri-Arroyo, Malloy L. Caeli, Tisha R. Reid, Laura A. Haunert, Heather A. O'Leary, Gerardo Maupome, David A. Haggstrom
Journal: Journal of Clinical Oncology (2021)

e22513 Background: Latinos are the fastest growing ethnic group in the US: cancer is the leading cause of death. Cancer screening is designed to decrease cancer-specific mortality among age- and gender-appropriate populations, but is implemented less frequently among Latino populations. Barriers to screening among Latinos are less well understood. Methods: A cross-sectional, online survey was used to assess perspective on cancer information-seeking behavior, demographic, economic, healthcare access and COVID-related factors among Latino adults (&gt;18) living in Indiana able to read and write in Spanish or English. Respondents were recruited using Facebook targeted advertisement and data were collected through Qualtrics. USPSTF recommendations for breast (BC), cervical (CC) and colorectal cancer (CRC) screening were used to evaluate screening adherence. The influence of explanatory variables on cancer-related outcomes was analyzed using univariate chi-squared tests for categorical variables and t-test for scale variables. Following this, significantly influential factors (p &lt; 0.05) were included in multivariate logistic regression models for each response variable. Model selection was performed using stepwise regression. Results: A total of 1624 respondents participated, with 832 (51.2%) completing the survey in Spanish. Median age was 52 years old (range 18-71) for English and 54 (18-77) for Spanish respondents. 80% of respondents were located in urban areas. Cancer screening adherence rates were 45.2% for BC, 61.8% for CC and 68.0% for CRC. The main factor associated with screening adherence across all malignancies (Table) was white self-identification, other factors included having children (OR: 1.79) and having received a COVID test (OR: 1.91) for CRC, having Spanish as chosen language for the survey for CC and BC respectively. Having higher income was associated with less adherence in CRC (OR: 0.50 when expressed as subjective income adequacy, compared with people finding difficult on present income) and CC (OR: 0.18 when expressed as &gt; 75,000 USD annual income, compared with 0-35,000 USD annual income). Conclusions: In this interim analysis of the largest Latino survey in Indiana, our findings were counter-intuitive regarding the association of income and language with cancer screening adherence. For income, these findings may have been due to lower out-of-pocket costs among vulnerable populations covered by Medicaid or Medicare insurance. For Spanish differences may be explained by increased language specific outreach for certain screening tests but not for others. Overall, these results highlight the necessity for targeted awareness campaigns for the Latino population in Indiana.[Table: see text]
Toxigenic Clostridium Difficile Colonization in Patients with Hematologic Malignancies Admitted to the Hospital for Chemotherapy or Hematopoietic Cell Transplantation
Authors: John L Vaughn, Misty Lamprecht, Ying Huang, Mirela Anghelina, Joan-Miquel Balada-Llasat, Zeinab El Boghdadly, Rachel Childs, Preeti Pancholi, Leslie A Andritsos
Journal: Blood (2017)
Features in genomics and tumor immune microenvironment in NSCLC treated with neoadjuvant PD-1 blockade.
Authors: Shuhang Wang, Ning Li, Beibei Mao, Jianming Ying, Xiuli Tao, Wei Tang, Lei Zhang, Xiao Geng, Fan Zhang, Qi Xue, Lijia Wu, Henghui Zhang, Shugeng Gao, Jie He
Journal: Journal of Clinical Oncology (2021)

9063 Background: Results from several clinical trials have preliminarily demonstrated the safety and effectiveness of single PD-1 inhibitors in neoadjuvant setting for resectable non-small cell lung cancer (NSCLC). However, only around 40% patients could achieve Major Pathological Response. How to select patients who could benefit from single PD-1 blockade remains elusive. Methods: In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden (TMB), copy number alteration (CNA, including copy number gain and loss) burden with the pathological response to neoadjuvant PD-1 blockade. We also evaluated the dynamic changes of tumor immune microenvironment (TIME) by analyzing pre-immunotherapy treatment tumor biopsy samples from twenty-nine NSCLC patients as well as the matched post-surgery samples after neoadjuvant sintilimab treatment and resection. Targeted DNA sequencing (543 genes), PD-L1 immunochemistry staining (22C3) and multiplex immunofluorescence (CD4, CD8, CD9) were applied. Results: The degree of pathological regression and major pathological response (MPR), were positively correlated with tumor proportion score (TPS) of PD-L1 (R = 0.40, p = 0.04) and negatively correlated with copy number gain (CNgain) burden (R = -0.44, p = 0.04). Of note, the combination of CNgain burden and TPS can better stratify MPR patients compared to CNgain or TPS alone. Whereas, TMB only had a marginal association with pathological response (R = 0.32, p = 0.15). Additionally, PD-1 blockade led to an increase in CD8 + PD-1-T cells in the tumor region (p = 0.04, Mann-Whitney U test for paired samples) and a reduction in Tregs and M2 macrophages in the stromal region (p &lt; 0.05, Mann-Whitney U test for paired samples). Further investigation showed that the degree of CD8 + PD-1-T cell increase was significantly associated with MPR (p &lt; 0.05, Mann-Whitney U test). Intriguingly, we also observed a substantial reduction in CD19 + cells in the non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC patients. Conclusions: TPS and CNgain burden were correlated with pathological response to neoadjuvant immunotherapy in NSCLC patients. This may provide potential selective indicators for future clinical trials of neoadjuvant immunotherapy. The dynamic changes of components in the tumor immune microenvironment may provide novel insight into the immune responses induced by neoadjuvant PD-1 blockade therapy.
Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Johannes Düll, Kami J. Maddocks, Eva Gonzalez-Barca, Wojciech Jurczak, Anna Marina Liberati, Aleš Obr, Gianluca Gaidano, Pau Abrisqueta, Marc André, Martin H. Dreyling, Tobias Menne, Maren Dirnberger-Hertweck, Johannes Weirather, Sumeet Vijay Ambarkhane, Gilles A. Salles
Journal: Journal of Clinical Oncology (2021)

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]
Genomic aberrations in African American patients with solid tumors: A comparative institutional study.
Authors: Manan Shah, Michelle Jeung-Eun Lee, Nicholas Hong, Sri Lakshmi Sudha Kollepara, James Lillard, Gabriela Oprea, Sanjay R. Jain
Journal: Journal of Clinical Oncology (2021)

e15086 Background: Genomic mutations play an important role in cancer pathogenesis and can be used as targeted agents for treatment. Cancer related biomarkers in body fluids and tissues are being used to identify specific target genes. They also help in predictive and prognostic assessment related to the disease. Various platforms like guardant 360, foundation act, oncotype are commercially available. Specific genomic aberrations have enhanced the field of Precision Medicine in individualizing treatment protocols. Methods: Prospective data was collected from 45 African American patients at our institution using the commercially available Genomic Enabled Medicine ExTra cancer panel (Ashion Analytics). Sample include 18 types of cancer (10 breast, 9 colorectal, 5 endometrium, 4 prostate, 3 uterine, 2 cervical, 1 pancreas, 1 gallbladder, 1 melanoma, 1 larynx, 1 gastric, 1 carcinoid, 1 carcinosarcoma, 1 lymphoma, 1 ovary, 1 bladder, 1 thyroid). Both tumor and normal DNA were collected from year 2019 through 2020. For comparison, clinical and genomic, The Cancer Genome Atlas (TCGA) data for 1,065 African American adults with solid tumors were downloaded from the NCI Genome Data Common portal. The two data sets were eventually compared for identifying common genetic mutations and possible new targets for cancer management. Results: Of the 45 patients, 38 patients (84%) had at least one genomic alteration, and 38 known driver mutations were identified. Their median age was 56 years (range, 37 – 94). TP53 mutations were most common, identified in 44% of patients versus 37% in African Americans in TCGA. PIK3CA and KRAS mutations were next most common (22% and 20%, respectively) compared to TCGA African American samples (13% and 12%, respectively). The most frequent mutations on PIK3C were H1047R in 4 patients (8.8%), followed by E545K in 3 patients (6.6%). Oncogenic mutations were observed in APC, PTEN, ARID1A, FBXW7, NF1, PIK3R1, RNF43, ATM, CCNE1. Conclusions: In our study, we found higher prevalence of oncogenic driver gene mutations (including TP53, PIK3CA, KRAS, APC, PTEN, ARID1A) in African American cancer patients compared to TCGA African American cancer patients. It is important to note that high percentage of our patients had actionable oncogenic drivers that may be useful in treatment decision-making. Our aim is to continue to build on our database on African American patients for identifying specific and common gene mutations to enhance development of targeted agents.
<i>Plasmodium falciparum</i> Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies
Authors: Abhai K. Tripathi, Miranda S. Oakley, Nitin Verma, Godfree Mlambo, Hong Zheng, Scott M. Meredith, Edward Essuman, Ankit Puri, Richard A. Skelton, Kazuyo Takeda, Victoria Majam, Isabella A. Quakyi, Emily Locke, Merribeth Morin, Kazutoyo Miura, Carole A. Long, Sanjai Kumar
Journal: Science Translational Medicine (2021)

Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success. By applying an unbiased transcriptomics-based approach, we have identified Pf77 and male development gene 1 (PfMDV-1) as two P. falciparum TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in Anopheles mosquito midguts in a standard membrane feeding assay. In-depth studies were performed to characterize the genetic diversity of, stage-specific expression by, and natural immunity to these two molecules to evaluate their suitability as TBV candidates. Pf77 and PfMDV-1 display limited antigenic polymorphism, are pan-developmentally expressed within the parasite, and induce naturally occurring antibodies in Ghanaian adults, which raises the prospect of natural boosting of vaccine-induced immune response in endemic regions. Together, these biological properties suggest that Pf77 and PfMDV-1 may warrant further investigation as TBV candidates.
EPCT-22 SAFETY AND EFFICACY OF INTRAVENTRICULAR IMMUNOVIROTHERAPY WITH ONCOLYTIC HSV-1 G207 FOR TREATMENT OF LEPTOMENINGEAL DISEASE
Authors: Kyung-Don Kang, Joshua Bernstock, Bryan Mott, Li Nan, Rong Li, Stacie Totsch, Sam Gary, Gelare Ghajar-Rahimi, Tina Etminan, Tanja Eisemann, Robert Wechsler-Reya, Elizabeth Beierle, George Gillespie, James Markert, Gregory Friedman
Journal: Neuro-Oncology (2021)

Abstract Leptomeningeal metastatic disease (LMD) occurs in 30–50% of newly diagnosed and recurrent pediatric malignant cerebellar tumors and 20–45% of malignant supratentorial tumors. Radiation and chemotherapy often cause substantial long-term neurotoxicity and outcomes remain poor for patients with LMD. At recurrence, LMD is generally minimally responsive to conventional therapies. Immunovirotherapy with engineered oncolytic HSV-1 G207 has emerged as a promising treatment for children with high-grade brain tumors. G207 infects and kills tumor cells while sparing normal cells and stimulates a robust anti-tumor immune response. Intratumoral G207 inoculation demonstrated safety and preliminary efficacy in a pediatric Phase 1 trial in recurrent/progressive high-grade glioma (NCT02457845), and a Phase 2 trial (NCT04482933) is forthcoming. Additionally, a Phase 1 trial of intratumoral G207 in recurrent/progressive malignant pediatric cerebellar tumors is ongoing (NCT03911388). While intratumoral inoculation delivers G207 directly to a primary tumor, it requires neurosurgical procedures thereby limiting repeat doses. Thus, we sought to establish the safety and efficacy of intraventricular G207. Utilizing an immunocompetent, HSV-sensitive murine strain, we determined that a standard 1x107 plaque-forming units (PFU) dose of G207 resulted in damage to the ependymal lining. However, interferon induction with an intraventricular low-dose (1x104 PFU) of G207 or polyinosinic-polycytidylic acid (poly I:C), a toll-like receptor 3 agonist, three days prior to standard treatment dose protected the ependymal lining. This approach enabled safe delivery of multiple subsequent doses. Importantly, with these protective measures, G207 significantly prolonged survival in pediatric patient-derived xenograft models and an immunocompetent murine LMD model of group 3 medulloblastoma, the most aggressive and fatal subtype. Collectively, these data indicate that toxicity from intraventricular G207 can be safely mitigated prior to a therapeutic dose, and that intraventricular G207 effectively targets group 3 medulloblastoma including LMD. These findings provide support for clinical translation of intraventricular G207.
Pathway use and concordance in affiliated academic and community oncology practices.
Authors: Stephen B. Edge, Lu Liu, Nessa Stefaniak, Allison Soucise, Saifuddin Soniwala, Saby George, Boris W. Kuvshinoff, David Tear, Monica L. Murphy, Mishellene McKinney
Journal: Journal of Clinical Oncology (2021)

e18639 Background: Clinical oncology pathways (COP) provide treatment (Rx) decision support and allow detailed quality oversight. There are limited data on use of COP and the proportion of patients receiving COP recommended Rx (concordant / “On Pathway” Rx – OnP) and on the reasons for COP non-concordant “Off Pathway” Rx (OffP). Methods: COP concordance and reasons for OffP Rx were evaluated and compared at an NCI-designated cancer center (Roswell Park Comprehensive Cancer Center – RP) and its 5 affiliated community practice sites (Roswell Park Care Network – RPCN) for COP Rx decisions from 10/1/19 – 9/30/20. Elsevier ClinicalPath Oncology COPs (formerly Via Oncology) were implemented in 2018 at RP and RPCN and are completed at initiation of any systemic Rx. COPs cover about 85% of cancers, excluding most hematologic cancers. COP Rx decisions are classified as OnP (including Rx on a clinical trial) or OffP. All OffP decisions are reviewed retrospectively to identify the reasons for OffP Rx. Differences in OnP rates at RP and RPCN were compared by chi square test or Fisher’s test overall and for 7 cancer type groups and for adjuvant Rx (ADJ) and metastatic disease (MET). ADJ/MET comparison excluded gynecologic cancer (GYN), myeloma and myelodysplastic syndrome (MDS) because COPs do not classify ADJ vs MET for these. Results: At RP there were 4,291 Rx decisions for 3,361 patients and at RPCN 1,349 Rx decisions for 1,198 patients. Breast cancer was the most common cancer type (18% of patients at RP and 36% at RPCN). Proportions of patients with GYN, melanoma, sarcoma, and GU cancers were higher at RP and similar for GI, thoracic and myeloma/MDS. Among 3,153 ADJ and MET Rx decisions at RP, 55% were for METS vs. 36% of 1,096 decisions in the RPCN. Pathway decision concordance (OnP) rates overall were 85% at RP and 89% at RPCN (p &lt; 0.01- Table). OnP rates for ADJ Rx were 89% at RP and 92% at RPCN (p = 0.05), and for MET 84% at RP and 86% at RPCN (p = 0.53). Most OffP Rx was for medically valid reasons including comorbidity, new/targeted therapies, and prior Rx precluding COP recommended Rx. Conclusions: COP concordance was slightly higher in community practice, potentially because newer therapies, patients with greater morbidities and more complex cancers are in the academic practice. RP had a higher proportion of MET cases consistent with the tertiary practice treating more advanced cancer. OffP Rx was higher with MET, likely related to the nuances of Rx of MET cancer and new therapies not yet in pathways. OffP Rx was fully justified in most cases.[Table: see text]
Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis
Authors: Shuchi Anand, Maria E. Montez-Rath, Jialin Han, Pablo Garcia, LinaCel Cadden, Patti Hunsader, Russell Kerschmann, Paul Beyer, Mary Dittrich, Geoffrey A. Block, Scott D. Boyd, Julie Parsonnet, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2021)

Data from hepatitis B[1][1] and influenza vaccination[2][2] studies indicate blunted and foreshortened response to immunization in patients receiving dialysis, raising the worrisome possibility that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine may also yield lower
Management impact of preoperative germline genetic testing in patients with breast cancer at the Lifespan Cancer Institute.
Authors: Kaitlyn P. Lew, Don S. Dizon, Chanika Phornphutkul, Cindy Benson, Doreen Leyden Wiggins, Mary Anne Anne Fenton, Charu Taneja, Lauren J. Massingham
Journal: Journal of Clinical Oncology (2021)

10523 Background: Breast cancer is a heterogenous disease and management is complex. Advances in next generation sequencing has allowed genetic testing to be more accessible. However, conveying results to patients and care team can be challenging due to various variant classifications. Diagnostic results have the potential to guide management. Nondiagnostic results can be misinterpreted. The extent to which preoperative genetic testing affects management of newly diagnosed breast cancer is unknown. Methods: Newly diagnosed breast cancer patients were identified via review of breast tumor board between May 2019 and March 2019 followed by chart review to collect detailed information. Results: 408 newly diagnosed breast cancer cases were queried. Genetic evaluation was recommended and completed in 68%, not recommended (did not meet NCCN criteria) in 30% and declined in 2.7%. The genetic evaluation recommended cohort was associated with a higher mastectomy rate in comparison with when not recommended (31% vs. 9%, p=0.0001). Of those who completed genetic testing: 12% harbored a pathogenic/likely pathogenic variant (PV/LPV), 26% had a nondiagnostic variant of uncertain significance (VUS) and 61% had negative testing. Comparison between nondiagnostic test results (negative and VUS) and diagnostic test results revealed significantly increased number of women in the diagnostic group who chose mastectomy over breast conservation therapy (BCT, nondiagnostic 20% vs diagnostic 39%, p=0.018). When negative, VUS, and PV/LPV were each independently analyzed, diagnostic test results again revealed a significantly increased number of mastectomies over BCT (p&lt;0.05). Comparison of surgical choices in nondiagnostic VUS vs. negative results was not significantly different (Table). Comparing the surgical timelines, completing a genetic evaluation did not affect surgery timing (mean 2.3 vs. 2.2 months, p&gt;0.5). Conclusions: Germline genetic testing in patients with newly diagnosed breast cancer impacts clinical management. Those harboring a diagnostic result were more likely to choose mastectomy over BCT. Not surprisingly, mastectomy rate was higher among those where genetic evaluation was recommended, possibly due to concerning personal or family history. The mastectomy rate was higher among those with a diagnostic result, indicating an understanding of the genetic testing significance by patients and the care team. More importantly, those who harbored nondiagnostic VUS did not make significantly different surgical choices compared with negative genetic testing, highlighting the critical role of proper genetic counseling and being part of the care team. We conclude consideration of genetic evaluation is clinically useful and feasible without affecting the surgical timeline.[Table: see text]