tbuckley/cabot-search huggingface dataset:
Granulomatous and sarcoid-like immune related adverse events (irAEs) in melanoma patients following CTLA4 blockade adjuvant therapy: An analysis of 1670 high-risk patients.
Authors: Arish Noor, Ibrahim Yassine, Sandra J. Lee, Megan Othus, James Moon, John M. Kirkwood, Vernon K. Sondak, Antoni Ribas, Kenneth F. Grossmann, Ahmad A. Tarhini
Journal: Journal of Clinical Oncology (2021)

9582 Background: Granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs following treatment with immune checkpoint inhibitors (ICIs) have been described in sporadic reports in the literature but the true incidence is unknown. Methods: We sought to estimate the incidence of GSL in the context of prospectively conducted ECOG-ACRIN E1609 phase III adjuvant trial in high-risk resected melanoma (N=1670 patients) testing ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose interferon-α (HDI). Descriptive statistics were used to calculate the incidence. Results: Among 1670 total patients treated with ICIs or with HDI in E1609, 1034 were treated with ipilimumab and 636 with HDI. Six GSL cases were reported among 1670 total patients treated with ipilimumab or with HDI as summarized in the table along with the corresponding CTCAE grades. More cases were observed with ipi10, followed by ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Conclusions: The incidence of granulomatous and sarcoid-like lesions (GSL) with adjuvant ipilimumab therapy in high-risk melanoma is rare. Reported cases ranged in grade from 1-3 and appeared manageable. Since most cases are asymptomatic, it is possible that GSLs are under-recognized and therefore, under-reported. A larger analysis including patients treated with anti-PD1 antibodies is currently underway. Clinical trial information: NCT01274338. [Table: see text]
Comparing of pan-cancer tumor immune microenvironment.
Authors: Jiaan Ye, Longgang Cui, Xiaochen Zhao, Guanghui Lan
Journal: Journal of Clinical Oncology (2021)

e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P &lt; 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8 + T cells and natural killer cell in tumor was statistically different. The proportion of CD8 + T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p &lt; 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p &lt; 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.
Initial reporting from the prospective National Cancer Institute (NCI) COVID-19 in Cancer Patients Study (NCCAPS).
Authors: Larissa A. Korde, Ana F. Best, Sacha Gnjatic, Andrea M. Denicoff, Grace E. Mishkin, Melissa Bowman, Lyndsay Harris, Ann M. Geiger, Worta J. McCaskill-Stevens, Stephen J. Chanock, Patricia Spears, Lawrence Rubinstein, Nicholas M. Mark, Jeremy Lyle Warner, Carmen Joseph Allegra, Adam J. Esbenshade, Michael V. Knopp, James H. Doroshow, Brian I. Rini
Journal: Journal of Clinical Oncology (2021)

6565 Background: Patients (pts) with cancer are at increased risk of SARS-CoV-2 infection and severe COVID-19 disease. Longitudinal follow-up is needed to characterize the severity, sequelae and outcomes in pts with cancer who develop COVID-19. Methods: NCCAPS is a prospective, longitudinal study (NCT04387656) aiming to accrue 2,000 pts with cancer undergoing active treatment or prior stem cell transplant for hematologic or solid tumor malignancy. Adult patients are eligible to enroll within 14 days of their first positive SARS-CoV-2 test; pediatric patients may also enroll retrospectively. Clinical data, patient-reported outcomes, blood specimens, and imaging are collected for up to 2 years. This abstract provides initial baseline and 2-month follow-up data. Results: As of Jan 22, 2021, 585 pts (552 adults and 33 pediatric pts) had complete baseline data and of these pts, 215 adults had 2 months of complete follow-up data. 23.4% of adults and 42.4% of pediatric pts were of non-White race and/or Hispanic/Latinx ethnicity. The most common cancer diagnoses were breast (19.6%), lung (9.9%) and multiple myeloma (8.9%) in adults and acute leukemia (AML/ALL; 63.6%) in children. The most recent treatment was chemotherapy in 38.2%, immunotherapy in 9.6%, and radiation in 5.4%. Median time from positive SARS-CoV-2 test to study enrollment was 10.5 days in adults and 18 days in pediatric pts. Preliminary analysis of plasma cytokines will be presented. At enrollment, 84.6% of adults had COVID-19 symptoms. 55.9% reported symptoms 2 weeks after their positive SARS-CoV-2 test; this fell to 39.0% at 1 month and 28.8% at 2 months (see Table). Of the 215 adults with complete data at 2 months, sequelae included pulmonary (n=22, 10%), cardiovascular (n=12, 6%) thromboembolic (n=9, 4%), bleeding (n=9, 4%) and gastrointestinal (n=11, 5%). 144 (67%) reported at least one cancer treatment disruption in the first 2 months, most commonly delayed therapy (n=98; 46%).Of the 348 adults with baseline data and SARS-CoV-2 test date prior to Nov 23, 2020, 6.3% had died (median time from SARS-CoV-2 test to death: 27 days), and 22.1% reported at least one hospitalization for COVID-19. No deaths were reported in the pediatric population. Conclusion: Cancer pts with COVID-19 report ongoing symptoms after acute infection and a substantial number develop sequelae. Cancer treatment disruptions are common in the initial months following SARS-CoV-2 infection. Longer follow-up will inform whether these treatment disruptions are associated with adverse outcomes. Clinical trial information: NCT04387656. [Table: see text]
Mammography screening disparities in Asian American women: Findings from the California Health Interview Survey 2015-2016.
Authors: Yannan Li, Hui Xie, Nicholas Theodoropoulos, Qian Wang
Journal: Journal of Clinical Oncology (2021)

e18568 Background: Foreign-born Asians were less likely to utilize preventive care due to medicine beliefs, language barriers, insurance coverage, and more. Their perceptions of breast cancer risks and screening benefits for asymptomatic conditions may differ from individuals born in the United States. It is urgent for preventive health professionals to understand screening disparities in Asian Americans. Methods: Data from the California Health Interview Survey (CHIS) 2015-2016 were used. Multivariable adjusted logistic regressions were generalized to identify the up-to-date mammography screening in relation to socioeconomic, chronic health condition/health behavior, and preventive care utilization, stratified by race. Results: Of NH-White and Asian American women aged 40 and above (unweighted N = 13,451), 78.41% were NH-White, 25.38% were foreign-born, 56.88% spoke only English at home, and 6.44% were not currently insured. The prevalence for self-reported mammography screening in NH-White and Asian American women were 68.06% and 65.97%, respectively. Among Asian American women, the lowest rate of mammograms was in Koreans (55.29%) and Chinese (72.19%) had the highest rate (p = 0.6438). In NH-White women, place of birth, smoking status, borderline diabetes, high blood pressure, is currently insured, and having a preventive care visit in the past 12 months were significant factors. Within Asian American women, borderline hypertension and having a preventive care visit were significant factors, but not ethnicity. Conclusions: The findings indicate that mammogram disparity in relation to socioeconomics, health behaviors, preventive care utilization, and race. Further development of ethnic-specific cancer prevention strategies and policies that address the subgroup differences within the larger racial/ethnic population are needed. Public health outreach and cancer education should target Asian American women with borderline hypertension and no preventive care visits.
Response to ‘Decline in the use of phototherapy in France from 2010 to 2019’
Authors: E. Eadie, M. Gallacher, A. Gorczynski, L. Smith, R.S. Dawe
Journal: British Journal of Dermatology (2021)

Linked Article: Aubin et al. Br J Dermatol 2021; 185:662–663.
The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia
Authors: Xing-chen Ding, Liang-liang Wang, Xue-dong Zhang, Jun-long Xu, Pei-feng Li, Hua Liang, Xian-bin Zhang, Li Xie, Zi-han Zhou, Jia Yang, Ralph R. Weichselbaum, Jin-ming Yu, Man Hu
Journal: Journal of Hematology & Oncology (2021)

Abstract Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8 + T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.
GERM-03. CLINICAL FEATURES AND OUTCOME OF CHILDREN WITH INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A POPULATION-BASED STUDY IN HONG KONG
Authors: Anthony P.Y. Liu, Dennis T L Ku, Eric Fu, Chung-Wing Luk, Jeffrey P W Yau, Siu-Cheung Ling, Godfrey C F Chan, Matthew M K Shing
Journal: Neuro-Oncology (2021)

Abstract The incidence of central nervous system non-germinomatous germ cell tumor (NGGCT) is four times higher in Chinese children than in the Western population. Reports on the outcome of Asian patients are nonetheless limited. Here we aim to summarize the experience of treating pediatric NGGCT in Hong Kong. Leveraging a population-wide pediatric oncology database, Chinese children with NGGCT diagnosed from 2002–2020 (n=43) were retrospectively studied. The diagnoses of NGGCT were made either with elevation in tumor markers (AFP/hCG; n=19), or by histology with/without concomitant raise in tumor markers (n=24). Most patients were treated with a combination of chemotherapy (cisplatin/etoposide/bleomycin, carboplatin/etoposide or carboplatin/etoposide/ifosfamide) and radiation (craniospinal+boost, whole ventricular+boost, or focal). The male:female ratio was 37:6, and the median age of diagnosis was 11.2 years. Primary tumor locations were pineal in 18, sellar/suprasellar in 12, basal ganglial in 9, supratentorial in 3 and posterior fossa in 1. Three had metastasis. Among the patients diagnosed by histology (n=24), 12 had mixed GCT, 8 had malignant/immature teratoma, 3 had embryonal carcinoma, and 1 had yolk sac tumor. With a median follow-up of 8 years, 8 patients progressed (local=7, distant=1), and 9 patients died (progression=5, palliative treatment for congenital tumors=2, sepsis=1, procedural complication=1). The respective 5-year PFS and OS were 74.9±6.9% and 82.2±6.1%. In multivariate analysis, high serum hCG level and no radiation use were significantly associated with inferior PFS. Outcome did not differ according to chemotherapeutic reagents used or radiation fields. Four patients had growing teratoma syndrome. Long-term neuroendocrine sequalae were common. In conclusion, children with NGGCT had reasonable outcome after multi-modal therapy in Hong Kong. Effort should be made to minimize tumor and treatment-related toxicities. The role of tumor markers for risk-stratification within NGGCT needs to be further interrogated.
Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.
Authors: Michael Grimm, Bhuvaneswari Ramaswamy, Maryam B. Lustberg, Robert Wesolowski, Sagar D. Sardesai, Jeffrey Bryan VanDeusen, Mathew Amprayil Cherian, Daniel G. Stover, Margaret Elena Gatti-Mays, Ashley Pariser, Mahmoud Kassem, Julie Stephens, Marilly Palettas, Nicole Olivia Williams
Journal: Journal of Clinical Oncology (2021)

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]
MicroRNA-497/195 is tumor suppressive and cooperates with CDKN2A/B in pediatric acute lymphoblastic leukemia
Authors: Elena Boldrin, Enrico Gaffo, Alexandra Niedermayer, Judith M. Boer, Martin Zimmermann, Dieter Weichenhan, Rainer Claus, Vera Münch, Qian Sun, Stefanie Enzenmüller, Felix Seyfried, Salih Demir, Julia Zinngrebe, Gunnar Cario, Martin Schrappe, Monique L. Den Boer, Christoph Plass, Klaus-Michael Debatin, Geertruij te Kronnie, Stefania Bortoluzzi, Lüder Hinrich Meyer
Journal: Blood (2021)
Study on the extract of Huangqi and Ezhu for the crosstalk of exosomes mediating tamoxifen resistance on LCC9 cells.
Authors: Shasha Cui, Dongni Zhang, Wenping Lu
Journal: Journal of Clinical Oncology (2021)

e12517 Background: Estrogen receptor (ER)-positive breast cancer is the most frequent subtype accounting for about 70% of all cases. Tamoxifen (TAM) is still the most effective drug for treating ER+/PR+ breast cancer. However, recurrence and metastasis still occur in 30-50% of patients due to TAM resistance. Furthermore, studies have shown that breast cancer stem cells (BCSCs) play an important role in TAM resistance, and exosomes regulate dynamic changes of BCSCs in tumor microenvironment. Additionally, the extract of Huangqi and Ezhu (EHE) has been shown to inhibit multiple TAM-associated resistance signaling pathways. In the current study, we investigated the effect of EHE to reverse TAM-resistance in LCC9 cells via crosstalk of distinct types of exosomes. Methods: Exosomes were extracted from LCC9 cells by ultracentrifugation and characterized by particle size detection, transmission electron microscopy and western blot analysis. Subsequently, isolated LCC9 exosomes were used to treat bone marrow stem cells (BMSCs) with EHE only, TAM only, EHE and TAM (EHETAM), and no treatment (negative control, NC). After treatment, exosomes of BMSCs were isolated and incubated further with LCC9 cells. CCK-8 assay and flow cytometry analysis were performed, and protein expression in treated LCC9 cells was tested by western blot analysis. Results: Data from CCK-8 assay showed that compared with the NC group, proliferation of LCC9 cells was significantly reduced in the presence of exosomes of BMSCs treated with TAM (82.9%, 77.1% , 75.4%), EHE (73.2 %, 69.5% , 68.2 %) and EHETAM (68.9 %, 52.3%，54.1% ) after 24h, 48h, and 72 h, respectively (p &lt; 0.001). EHE and EHETAM groups have more effective inhibition on cell proliferation than TAM only group on the different time separately(p &lt; 0.001).Flow cytometry analysis demonstrated that compared with the NC group(6.1%), increased apoptosis was observed for groups of TAM (8.1%), EHE (12.5%) and EHETAM (12.2%) (p &lt; 0.001). Compared with TAM only group, EHE and EHETAM groups also have significantly higher cell death rate (p &lt; 0.001). Lower CD44 and HER2 expression and higher ERα expression were observed in EHE, TAM, and EHETAM than those of NC group by western blot analysis of treated LCC9 cells. Conclusions: EHE treatment can reverse TAM-resistance by interfering with the crosstalk between BMSCs and breast cancer cells exosomes to induce more active apoptosis and reduce TAM-resistant CD44+ cancer stem cells.
Levels of some cytokines in tumors of ovarian cancer patients with different responses to platinum-containing chemotherapy.
Authors: Aleksandr B. Sagakyants, Oksana G. Shulgina, Darya Yu. Yakubova, Elena P. Ulianova, Galina V. Zhukova, Anna P. Menshenina, Inna A. Novikova, Ekaterina V. Verenikina, Tatiana G. Chalabova
Journal: Journal of Clinical Oncology (2021)

e17528 Background: Resistance to chemotherapy is a complex problem in the treatment of patients with ovarian cancer (OC). Various intercellular intermediates are involved in the phenomenon, and cytokines are the most important of them; however, the involvement of individual representatives in the processes is poorly understood. Our purpose was to analyze levels of some cytokines in tumors of OC patients with different responses to chemotherapy they receive. Methods: Samples of ovarian tumors were obtained from 100 patients (aged 29-79 years) with advanced ovarian cancer stage IIIC-IV with/without ascites. All patients recruited in 2016-2020 received standard combination treatment with surgery and platinum-containing polychemotherapy (Pt CT). Based on the results of neoadjuvant Pt CT, patients were divided into groups: patients with stabilization or progression–group 1 “without effect”; patients with complete/partial regression–group 2 with positive effect. All patients gave their informed consent for the study. Levels of IL-6, IL-8 and IL-10 were measured in cytosolic fractions of tissue samples using standard ELISA test systems (Vektor-Best, Russia). Results were presented as Me (LQ; UQ). The significance of differences between the samples was assessed using the Mann-Whitney test (the differences were considered significant at p&lt;0.05). Results: Levels of the anti-inflammatory cytokine IL-10 in tumors of patients did not differ significantly between groups 1 and 2. The local levels of IL-6 in tumors of patients sensitive to Pt CT were 5.5 times higher than in resistant patients–2.41 (1.71;4.55) vs. 0.44 (0.26;1.04), p≤0.05, and IL-8 13 was 13 times higher–27.23 (4.01; 30) vs. 2.1 (1.72; 2.5), p≤0.05. Conclusions: Local levels of anti-inflammatory cytokines IL-6 and IL-8 were significantly higher in patients with sensitivity to platinum-containing chemotherapy, which may reflect characteristics of the microenvironment in OC tumor tissues, while IL-10 levels were similar in all patients. The revealed features of the cytokine profile may be one of the factors determining the treatment outcomes.
Cold Pain Causes the Greatest Drop in Microvascular Blood Flow in Sickle Cell Disease Subjects and Normal Controls Exposed to Graded Thermal Stimuli
Authors: Saranya Veluswamy, Payal Shah, Maha Khaleel, Mammen Puliyel, Wanwara Thuptimdang, Patjanaporn Chalacheva, John Sunwoo, Roberta Miyeko Kato, Jon A Detterich, John C Wood, Jennie Tsao, Lonnie Zeltzer, Richard Sposto, Michael Khoo, Thomas D. Coates
Journal: Blood (2017)