tbuckley/cabot-search huggingface dataset:
Sociodemographic and clinicopathologic features of elderly breast cancer patients in Brazil: A sub-analysis of AMAZONA III study (GBCAM 0115).
Authors: Carla Pavei, Daniela Dornelles Rosa, Jose Bines, Gustavo Werutsky, Carlos H. Barrios, Eduardo Cronemberger, Sergio D. Simon, Geraldo Silva Queiroz, Vladmir Claudio Cordeiro De Lima, Ruffo Freitas-Junior, Heloisa Magda Resende, Susanne C. Costa, Tomas Reinert, Brigitte M. Van Eyll, Vanessa Dybal Bertoni, Yeni Verónica Neron, Nicolas Lazaretti, Rafaela Gomes, Taiane Francieli Rebelatto, Pedro Emanuel Rubini Liedke
Journal: Journal of Clinical Oncology (2021)

e12603 Background: Breast cancer (BC) is the most common invasive cancer diagnosed in women worldwide. The risk of developing BC increases with age. Studies have shown that approximately up to half of BC cases occur in patients aged 65 years and older. To better understand and characterize elderly patients with BC in Brazil, we performed a sub analysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973). Methods: The AMAZONA III study (GBCAM 0115) is a prospective cohort study that included 2,950 women with newly diagnosed invasive BC from January 2016 to March 2018 in 23 Brazilian sites. For this sub analysis, only BC patients aged 65 years and older were included. To compare sociodemographic and clinicopathologic features we classify patients into two groups: cohort 65 to 75 years of age and cohort 75 years and older. Qualitative variables were described by absolute and relative frequencies and compared with Chi-square test. Results: Of 2,950 BC patients from AMAZONA IIII study, 602 (20.8%) were ≥ 65 years-old and were included in this sub analysis. Most patients (93.1%) had ECOG performance status 0-1, 63.4% were white. In terms of educational level, 68.6% had reported completing primary school or less. At diagnosis, 23.7% of patients had clinical stage (CS) I, 41.9% had CS II, 28.2% had CS III, and 6.2% had CS IV disease. The majority of BC were detected by symptoms and only 34.2% were detected by screening. Regarding pathological characteristics, half of cases were grade 2, 58.7% were hormone receptor positive, 25% were HER-2 positive, and 16.0% were triple negative. When evaluated by subgroup, patients from cohort 75 years and older were more frequently diagnosed at advanced clinical stages and had worse ECOG performance status at diagnosis. There was no statistically significant difference in molecular subtype, tumor grade, and mode of BC detection (Table). Conclusions: Elderly patients commonly had BC detected by symptoms. Patients from cohort 75 years and older are diagnosed more frequently with advanced disease and worse performance status than patients from cohort 65 to 75 years. Strategies to improve BC screening and educational programs among elderly patients are warranted to guarantee accessibility to early BC diagnosis.[Table: see text]
A registry-based, observational safety study of inotuzumab ozogamicin (InO) treatment in patients (pts) with B-cell precursor acute lymphoblastic leukemia (ALL) who proceeded to hematopoietic stem cell transplant (HSCT).
Authors: Marcos J.G. De Lima, Partow Kebriaei, Francesco Lanza, Christina Cho, Sergio Giralt, Gizelle Popradi, Michael T Hemmer, Xin Zhang, Richa Shah, Verna L. Welch, Erik Vandendries, Matthias Stelljes, David I. Marks, Wael Saber
Journal: Journal of Clinical Oncology (2021)

7017 Background: InO is a CD22-directed antibody-drug conjugate indicated for treatment of relapsed/refractory (R/R) ALL. InO has been associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly post-HSCT. Registry data (Center for International Blood and Marrow Transplant Research [CIBMTR]) was analyzed to assess toxicity in pts with ALL who received InO prior to HSCT. Methods: CIBMTR patient data are being collected for a 5-year period after US approval of InO (Aug 2017 – Aug 2022). Data from US pts age ≥18 y treated with InO who proceeded to allogeneic HSCT were included. Using interim data at 3 y, we evaluated post-HSCT outcomes, including clinical status, overall survival, transplant-related (non-relapse) mortality (NRM), relapse, death after relapse (time from HSCT to death after the first 28 d from any cause with prior relapse/progression post-HSCT), and investigator-defined adverse events, including hepatic VOD/SOS. All statistical analyses are descriptive. Results: Data accrued from 18 Aug 2017 to 17 Aug 2020 for 131 adult pts (median age 40 y) who proceeded to first allogeneic HSCT: 31% in first complete remission (CR1), 46% in CR2, 13% in ≥CR3, 5% in 1st relapse, 2% in ≥3rd relapse, and 3% in primary induction failure. A majority (70%) had transplants from peripheral blood stem cells, and 47% involved an HLA-identical sibling or other related donor. Nearly half received myeloablative conditioning regimens. Before HSCT, 36% of pts received 1 cycle of InO, 46% had 2 cycles, and 17% had ≥3 cycles. Half (48%) received InO as a single agent. Median time from last dose of InO to HSCT was 2.0 mo (range: 0.4–26.2). At time of data-lock (11 Nov 2020), post-transplant data were available for 131 pts. Outcomes for these pts are shown in the Table. Among a subgroup of adults with active R/R ALL (n = 91) at time of HSCT (median of 4 lines prior therapy), VOD/SOS incidence within 100 d of HSCT was 18%. Conclusions: Incidence of VOD/SOS after first HSCT in InO-treated pts with R/R ALL in this study was similar to the 18–19% reported in pooled analyses of 2 clinical trials among InO-treated pts with R/R ALL (Marks et al, Biol Blood Marrow Transplant 2019) and in the INOVATE study (Kantarjian et al, Lancet Haematol 2017). The NRM at 1 y of 21% (23% R/R ALL) is lower than the NRM at 1 y of 38% reported in the pooled analyses of R/R ALL InO recipients.[Table: see text]
American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID‐19 Pandemic: Version 2
Authors: Dawn M. Wahezi, Mindy S. Lo, Tamar B. Rubinstein, Sarah Ringold, Stacy P. Ardoin, Kevin J. Downes, Karla B. Jones, Ronald M. Laxer, Rebecca Pellet Madan, Amy S. Mudano, Amy S. Turner, David R. Karp, Jay J. Mehta
Journal: Arthritis & Rheumatology (2021)

Objective To provide clinical guidance to rheumatology providers who treat children with pediatric rheumatic disease (PRD) in the context of the coronavirus disease 2019 (COVID‐19) pandemic. Methods The task force, consisting of 7 pediatric rheumatologists, 2 pediatric infectious disease physicians, 1 adult rheumatologist, and 1 pediatric nurse practitioner, was convened on May 21, 2020. Clinical questions and subsequent guidance statements were drafted based on a review of the queries posed by the patients as well as the families and healthcare providers of children with PRD. An evidence report was generated and disseminated to task force members to assist with 3 rounds of asynchronous, anonymous voting by email using a modified Delphi approach. Voting was completed using a 9‐point numeric scoring system with predefined levels of agreement (categorized as disagreement, uncertainty, or agreement, with median scores of 1–3, 4–6, and 7–9, respectively) and consensus (categorized as low, moderate, or high). To be approved as a guidance statement, median vote ratings were required to fall into the highest tertile for agreement, with either moderate or high levels of consensus. Results To date, 39 guidance statements have been approved by the task force. Those with similar recommendations were combined to form a total of 33 final guidance statements, all of which received median vote ratings within the highest tertile of agreement and were associated with either moderate consensus (n = 5) or high consensus (n = 28). Conclusion These guidance statements have been generated based on review of the available literature, indicating that children with PRD do not appear to be at increased risk for susceptibility to SARS–CoV‐2 infection. This guidance is presented as a “living document,” recognizing that the literature on COVID‐19 is rapidly evolving, with future updates anticipated.
Polydatin reduces cardiotoxicity of tyrosine kinase inhibitor sunitinib by decreasing pro-oxidative stress, pro-inflammatory cytokines and NLRP3 inflammasome expression.
Authors: Massimiliano Berretta, Vincenzo Quagliariello, Simona Buccolo, Martina Iovine, Michelino De Laurentiis, Ernesta Cavalcanti, Raffaele Di Francia, Rosaria Taibi, Monica Montopoli, Gerardo Botti, Nicola Maurea
Journal: Journal of Clinical Oncology (2021)

e15065 Background: : Polydatin has anticancer and anti-inflammatory properties, however no studies investigated on its putative cardioprotective effects against anticancer therapies. Sunitinib, a recently-approved, multi-targeted tyrosine kinases inhibitor, prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. We investigated on the reduction of cytokines and growth factors of polydatin resulting in putative cardioprotective effects. Methods: Human fetal cardiomyocytes were untreated (control) or treated for 48 h with polydatin (50,100,200 and 400 µM) or sunitinib (5,10,25 and 50 µM) alone or combined to polydatin. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Exposure of adult cardiomyocytes to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly intracellular reactive oxygen species, lipid peroxidation and cytochrome c release from mitochondria leading to a reduction in cell death compared to cells exposed to sunitinib alone. Polydatin reduces expression of pro-inflammatory cytokines and growth factors involved in myocardial damages and down-regulates the signaling pathway of NLRP3 inflammasome and NF-κB, increasing cellular resistance to sunitinib-mediated damages. Conclusions: Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, has cardioprotective and anti-inflammatory properties, thus indicating one the mechanism(s) by which this metabolite of resveratrol might decrease sunitinib-mediated cardiotoxicity.
Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: Efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial.
Authors: Rodney Paul Rocconi, Sharad A. Ghamande, Minal A. Barve, Erin E. Stevens, Phylicia Aaron, Laura Stanbery, Ernest Bognar, Luisa Manning, John J. Nemunaitis, David M. O'Malley, Thomas J. Herzog, Bradley J. Monk, Robert L. Coleman
Journal: Journal of Clinical Oncology (2021)

5502 Background: In the VITAL (NCT02346747) trial, maintenance therapy with Vigil, an autologous tumor cell vaccine transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin for TGFβ expression control, following frontline platinum-based chemotherapy led to a recurrence-free survival (RFS) benefit in patients with advanced high-grade ovarian cancer (HR=0.69, 90% CI 0.44–1.07, p=0.078) and significantly in BRCA-wt patients (HR=0.51, 90% CI 0.30-0.88, p=0.020) ( Rocconi et al. Lancet Oncol. 2020). Here we report post-hoc HR deficiency (HRD) subgroup analysis and identification of an additional molecular subgroup sensitive to Vigil therapy involving STRING analysis. Methods: This double-blind, placebo-controlled, Phase 2b study randomized 92 patients with newly diagnosed stage III/IV ovarian cancer with a complete clinical response (CR) to frontline surgery and chemotherapy. Patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses or disease progression. RFS was the primary endpoint assessed by blinded independent central review. HRD status was determined according to the Myriad Genetics myChoice CDx assay (HRD score &lt; 42 for proficient). Using tumor annotated DNA polymorphism data, a protein-protein interaction network was constructed using the STRING database. Properties of this network including topological distance and the identification of hub genes were used to predict a target molecular population sensitive to Vigil. Results: In the per-protocol population (PP, n=91), 62 BRCA-wt patients were tested for HRD status. Forty-five patients were HR proficient (HRP) and 17 patients were HR deficient (HRD). No HRP patients in the Vigil group reported treatment related Grade 3 or higher adverse events. From the time of study randomization median RFS was improved with Vigil (n=25) in HRP patients compared to placebo (n=20) (Table 1). Similarly, overall survival (OS) benefit was observed in the Vigil group compared to placebo (Table 1). Improved RFS was demonstrated for a subset of patients with STRING predicted molecular profile. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed clinical benefit in both BRCA-wt and HRP molecular profile patients. Results suggest a unique molecular network that enhances sensitivity to Vigil therapy. Clinical trial information: NCT02346747. [Table: see text]
A phase II trial of stereotactic radiation therapy and <i>in situ</i> oncolytic virus therapy in metastatic triple-negative breast cancer (mTNBC) patients followed by pembrolizumab (STOMP).
Authors: Kai Sun, Joe E. Ensor, Yitian Xu, Licheng Zhang, Carlo Guerrero, Polly Ann Niravath, Tejal Amar Patel, Charles E. Geyer, Dharamvir Jain, Bin S. Teh, Andrew M. Farach, Mark Sultenfuss, Nakul Gupta, Mary R. Schwartz, Susan Haley, Jamie Mejia, E. Brian Butler, Eric Bernicker, Shu-Hsia Chen, Jenny Chee Ning Chang
Journal: Journal of Clinical Oncology (2021)

1079 Background: Pembrolizumab, stereotactic body radiotherapy (SBRT), and viral vector-based gene therapy such as adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus ganciclovir have each shown antitumor immune activity. The combination of those modalities may represent a window of opportunity to enhance pembrolizumab efficacy in mTNBC patients. Methods: In this single-arm, open-label phase II trial, mTNBC patients were treated with in situ oncolytic ADV/HSV-tk (5 x 10 11 vp) intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab until progression or intolerable toxicity. Response was assessed in non-irradiated metastatic sites. The primary end point was clinical benefit rate (CR, PR and SD per RECIST version1.1). Secondary endpoints included duration on treatment (DoT) and safety. Immune correlative analysis with peripheral blood CYTOF (D1 baseline, D7 and D38), and tissue imaging mass cytometry (IMC) with 35 cell surface markers was performed on paired biopsies (D1 baseline and D17). Results: 28 mTNBC patients were enrolled; 18 (64.3%) had PD-L1 negative tumors. Median age was 54 years (range 34-78). Median prior lines of chemotherapy were 2 (range 0-6), with 8 (28.6%) having received &gt;3. 3 (10.7%) had brain metastases. Clinical benefit was seen in 6 (21.43%) patients; 2 CR (7.1%),1 PR (3.57%) and 3 SD (10.7%). Patients who had clinical benefits had durable responses, with median DoT of 383 days (range 195-1195). One patient who had CR, but discontinued pembrolizumab due to Grade 3 pneumonitis, has remained disease free without any systemic therapy for 39 months. The combination was well tolerated; 9 (32.1%) patients had Grade 3- 4 AEs. Pre- and post-therapy CYTOF analysis showed significant association between immune biomarkers with clinical responses (AUC 0.75, Cohen’s Kappa 0.364). Tumor PDL1 was independently associated with response (AUC 0.70, Cohen’s Kappa 0.347); AUC for PDL1 together with immune biomarkers is 0.85. Conclusions: ADV/HSV-tk gene therapy followed by radiation therapy and then pembrolizumab is a well-tolerated promising treatment in heavily pretreated mTNBC patients. Early detection of increased effector and effector memory CD8 T cells and nonclassical monocytes correlates with response and non-response respectively. Clinical trial information: NCT03295916 .[Table: see text]
Associations of quality of social support and beliefs in curability among older adults with advanced cancer.
Authors: Lee Kehoe, Michael Sohn, Lu Wang, Supriya Gupta Mohile, Amita Patil, Megan Wells, Sandy Plumb, Yiping Pang, Nikesha Gilmore, Amber Kleckner, Elizabeth Belcher, Abdi Gudina, Brian Leslie Burnette, Thomas Paul Bradley, Nataliya Melnyk, Kah Poh Loh
Journal: Journal of Clinical Oncology (2021)

12049 Background: Prior studies suggest that social support plays a role in disease understanding of older patients with advanced cancer. In this study, we examined the association of quantity and quality of social support with belief in curability among older patients with advanced incurable cancer. Methods: We performed a secondary analysis of a cluster-randomized geriatric assessment trial (URCC 13070: PI Mohile) that recruited older adults (≥70) with advanced incurable cancer and caregivers. At enrollment, patients completed the Older Americans Resources and Services (OARS) Medical Social Support form to measure both quantity (number of close friends and relatives) and quality of social support. Quality of social support was measured using twelve questions, each ranged from 1 (none of the time) to 5 (all of the time). Higher cumulative scores indicated greater quality of support. For beliefs in curability, patients were asked, “What do you believe are the chances that your cancer will go away and never come back with treatment?” Responses were 0%, &lt;50%, 50/50, &gt;50%, and 100%. Ordinal logistic regression was used to investigate the association of social support with beliefs in curability, adjusting for adjusting for age, gender, education, race, number of Geriatric Assessment (GA) impairments, cancer type, and locality (rural versus urban). Results: We included 347 patients; mean age was 76.4 years, 91% were white, 52% were male, 46% had household income &lt;$50,000, and 55% had high school degree or higher. For every unit increase in OARS Medical Social Support score, the odds of believing in curability decreases by 36.4% [Adjusted Odds Ratio (AOR) 0.733, 95% Confidence Interval (CI): (0.555, 0.969)], after controlling for covariates. Quantity of social support was not associated with belief in curability [AOR 1.033 95% CI: (0.921, 1.156)]. Conclusions: Our study revealed that older patients with advanced cancer who felt more supported by their social network were more likely to report that their cancer was not curable. Interventions that improve quality of social support may also affect disease understanding. Funding: Patient-Centered Outcomes Research Institute (PCORI) 4634 and NIH K24 AG056589 to SGM, NCI UG1CA189961, T32CA102618, NCI K99CA237744 to Loh.
The Role of Medical Schools in Propagating Physician Bias
Authors: Jaya Aysola, Sanjna L Surya, David S Jones
Journal: New England Journal of Medicine (2021)

To the Editor: Amutah et al. (March 4 issue) 1 propose three methods for tackling the misrepresentation of race in medical education.We would like to suggest a fourth: ensuring equitable imagery in medical textbooks.Textbooks are often students' first point of engagement with medical conditions and thus provide the foundation for the development of biases that affect future interactions.One U.S. study showed that light skin tone was overrepresented in three quarters of textbooks. 2In depicting conditions in only one racial group, we risk the possibility that future physicians may not consider these conditions in assessments of patients who are members of other racial groups or who are of mixed race.As Amutah et al. suggest, in order to shape student understanding and minimize bias, it is vital for learning materials to include representative samples of the population and to reflect the details of the social and environmental factors associated with apparent racial differences in health and disease.Textbooks should be a substantive part of the fight against inequities in the provision of health care.They have the potential to help us move toward an antiracist community of health care providers.
Relationship between DICER1 mutations and immunotherapy biomarkers in solid tumors.
Authors: Jie Gao, Xia You, Taiyan Guo, Qin Zhang, Qianqian Duan, Chuang Qi
Journal: Journal of Clinical Oncology (2021)

2603 Background: Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults, and patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers. DICER1 is the core caner-intrinsic CTL-evasion gene, especially positive correlate with innate anti-PD-1 resistance signature or IPRES signature and hERV expression which involved in sensitivity and resistance to ICIs. Nevertheless, the association between mutations in DICER1 and the Chinese patients, the relationship between DICER1 mutations with immunotherapy biomarkers are unknown. Methods: NGS and clinical data were collected from 10953 Western pan-cancer patients (TCGA cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 3514 Chinese pan-cancer patients (Chinese cohort). Both DICER1 mutation ratio and TMB were calculated on the two cohorts following the same criteria.DNA NGS testing (MSI-high vs low/stable (MSS)) in Chinese cohort were included. NGS data of 3514 patients who also detected PD-L1 expression from Chinese clinical dataset were analyzed to explore the association with mutation and PD-L1. The survival information was collected from 1661 pan-cancer patients to analyze the association between DICER1 mutation and efficacy of immunotherapy (MSKCC cohort). Results: In total, 2.91% (319/10953) patients in TCGA harbored DICER1 mutation; in the Chinese cohort, the DICER1 mutation ratio (2.67%, 94/3514) was similar to TCGA. The top 5 mutant DICER1-associated cancer types in Chinese cohort were lung cancer, colon adenocarcinoma, liver cancer, uterine corpus endometrial carcinoma, melanoma. In both cohorts, TMB level of mutation group was significantly higher than wild-type group (p &lt; 0.001). The ration of mutation group in MSI-H (50%) and MSI-L (23.53%) was significantly higher than wild-type group in Chinese cohort (2.17%) (p &lt; 0.001). In addition, the ratio of PD-L1 positive expression (≥1%) in mutation group (48.94%, 46/48) was significantly higher than wild-type in Chinese cohort (38.48%,1316/2104) (p &lt; 0.05). The survival probability of mutation group was significantly longer than wild-type group in immunotherapy. Conclusions: The results indicated that DICER1 mutation was associated with a higher TMB, MSI-H and PD-L1 expression level in Chinese patients. Patients with DICER1 mutations may benefit more from ICIs.