tbuckley/cabot-search huggingface dataset:
A phase I/II study of bintrafusp alfa and NHS-IL12 in combination with docetaxel in adults with metastatic castration sensitive (mCSPC) and castration-resistant prostate cancer (mCRPC).
Authors: Mohammad O. Atiq, Marijo Bilusic, Fatima Karzai, Lisa M. Cordes, Julius Strauss, Houssein Abdul Sater, Jason Redman, Charalampos S. Floudas, James W. Hodge, Sofia Gameiro, William Douglas Figg, Jeffrey Schlom, William L. Dahut, James L. Gulley, Ravi Amrit Madan
Journal: Journal of Clinical Oncology (2021)

TPS5096 Background: Immune checkpoint inhibition is successful in a small subpopulation of men with prostate cancer. This could be related to barriers to immune response in the tumor microenvironment. Immunocytokines present an opportunity to specifically target the pleiotropic tumor microenvironment impacting immune cells beyond T-cells. NHS-IL12 is an immunocytokine that carries IL-12 (shown to impact natural killer and myeloid cells) and binds to necrotic tissue with exposed histones. Phase 1 studies have indicated immune and even PSA responses in prostate cancer to NHS-IL12 (Strauss J, CCR 2019). Preclinical data has demonstrated synergy with docetaxel, which is standard therapy in both mCSPC and mCRPC. Further synergy has been shown with a novel first-in-class bifunctional fusion protein (bintrafusp alfa) composed of the extracellular domain of human TGF-β receptor II (TGFβRII), which effectively functions to sequester or “trap” all three TGF-β isoforms (Lind H, JITC 2020), fused to a monoclonal antibody against PD-L1. This study will examine the potential of a novel combination of chemotherapy, checkpoint inhibition, and immunocytokines in metastatic prostate cancer. Methods: The study will evaluate safety of NHS-IL12 with docetaxel at escalating doses followed by the addition of bintrafusp alfa in all metastatic patients. Once safety of the combination is established, patients will enroll in 2 cohorts with either mCSPC or mCRPC. Eligible patients include mCSPC (≤134 days of starting ADT) and mCRPC (must have been previously treated with abiraterone or enzalutamide), with good performance status (ECOG of ≤ 2). Patients with brain metastases or who are immunocompromised are excluded. For mCSPC, the primary endpoint will evaluate the increase in the proportion of patients who have a PSA less than 0.2 ng/mL 7 months after the start of ADT, which is based on the prognostic value of PSA less than 0.2 ng/mL at 7 months in mCSPC (Harshman L, JCO 2017). The secondary endpoint is biochemical and radiographic time to progression. The primary endpoint for the mCRPC patients will evaluate progression free survival with secondary endpoints examining the percentage of patients with a 50% PSA decline from baseline and radiographic response rates per RECIST. Exploratory analysis will analyze changes in immune cell subsets after treatment as well as immune status of the tumor microenvironment. Clinical trial information: NCT04633252.
Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.
Authors: Xinlu Liu, Jiasheng Xu, Jian Sun, Deng Wei, Xinsheng Zhang, Danhua Wang, Tonghui Ma
Journal: Journal of Clinical Oncology (2021)

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P&gt; 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P&lt; 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P&lt; 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.
Consistent Alterations of Human Fecal Microbes After Transplantation into Germ-Free Mice
Authors: Yanze Li, Wenming Cao, Na L Gao, Xing-Ming Zhao, Wei-Hua Chen
Journal: Genomics Proteomics & Bioinformatics (2021)

Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human-mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as "variable taxa"). Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.
Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development
Authors: Daniel Alameda, Ibai Goicoechea, Marco Vicari, Elena Arriazu, Alice Nevone, Sara Rodriguez, Marta Lasa, Noemi Puig, Maria Teresa Cedena, Diego Alignani, Sonia Garate, David Lara-Astiaso, Amaia Vilas-Zornoza, Sarai Sarvide, Enrique M. Ocio, Ramon Lecumberri, Alfonso Garcia de Coca, Jorge Labrador, Maria-Esther Gonzalez, Luis Palomera, Mercedes Gironella, Valentin Cabañas, Maria Casanova, Albert Oriol, Isabel Krsnik, Albert Perez-Montaña, Javier de la Rubia, Jose-Enrique de la Puerta, Felipe de Arriba, Vito Michele Fazio, Joaquin Martinez-Lopez, Juan-Jose Lahuerta, Maria-Victoria Mateos, Maria-Dolores Odero, Felipe Prosper, Assaf Weiner, Ido Amit, Mario Nuvolone, Jesus F. San Miguel, Bruno Paiva
Journal: Blood (2021)
Incidence of SARS-CoV-2 Infection in Health Care Workers After a Single Dose of mRNA-1273 Vaccine
Authors: Kalpana Gupta, William J. O’Brien, Pamela Bellino, Katherine Linsenmeyer, Sucheta J. Doshi, Robert S. Sprague, Michael E. Charness
Journal: JAMA Network Open (2021)

This cohort study of health care workers in a metropolitan Veterans Administration network examines the association of SARS-CoV-2 infection after receiving a single dose of mRNA-1273 vaccine compared with no vaccination.
Outcomes for cancer patients on systemic anti-cancer therapies during the COVID-19 pandemic from the CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London) cohort study.
Authors: Valerie Crolley, Daire Hanna, Nalinie Joharatnam-Hogan, Neha Chopra, Ekin Bamac, Meera Desai, Yuk-Chun Lam, Sabiq Dipro, Ruhi Kanani, Jack Benson, William Wilson, Thomas Andrew Fox, Kai-Keen Shiu, Martin Forster, John A. Bridgewater, Daniel Hochhauser, Khurum Hayat Khan
Journal: Journal of Clinical Oncology (2021)

10567 Background: One of the major challenges with COVID-19 has been the changes to cancer services, including changes to the type of systemic anti-cancer treatment being delivered to patients. There needs to be a better understanding of which cancer patients are at the greatest amount of risk to make informed decisions on how cancer treatment can be altered to protect patients from COVID-19 infection. The CAPITOL (COVID-19 CAncer PatIenT Outcomes in North London) study investigated the outcomes of patients receiving systemic anti-cancer therapies (SACT) with regards to COVID-19 infection, as patients with cancer are hypothesised to be at higher risk. Methods: CAPITOL collected data from all patients receiving SACT at two cancer centres. The effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT was the primary outcome, and we used univariable and multivariable models in our analysis, adjusting for age, gender and comorbidities. Results: 2871 patients were analysed from 2nd March to 31st May 2020, all of whom received SACT; during this time period 68 (2.4%) were diagnosed with COVID-19. Receiving SACT increased the risk of death when contracting COVID-19 (adjusted (adj.) OR 9.84; 95% CI 5.73 – 16.9). The risk of contracting COVID-19 was increased by receiving chemotherapy (adj. OR 2.99; 95% CI = 1.72 - 5.21), with the risk significantly increased by high dose chemotherapy (adj. OR 2.36, 95% CI 1.35 – 6.48). Patients with comorbidities (adjusted OR 2.29; 95% CI 1.19 - 4.38), or with a respiratory or intrathoracic neoplasm (adj. OR 2.12; 95% CI 1.04 - 4.36) were also at increased risk of contracting COVID-19. Cancer patients who received targeted treatment had a reduced risk of contracting COVID-19 (adj. OR 0.53; 95% CI 0.30 – 0.95), while there was no significant change in risk caused by treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers. Conclusions: To the best of our knowledge, this is one of the first investigations into the risk of contracting COVID-19 in a cohort of all cancer patients on SACT. We found that patients on SACT are more likely to die if they contract COVID-19. The type of SACT received by cancer patients can affect their likelihood of contacting COVID-19, with chemotherapy increasing risk, targeted therapy decreasing risk and a potential protective effect for hormonal and immunotherapy.
Abstract #3989: Combined Resveratrol and radiation therapy in head and neck cancer
Authors: Robert Sclafani, Sunitha Siriwardana, Barbara Frederick, Simone Stahringer, Alpna Tyagi, Antonio Jimeno, Rajesh Agarwal, David Raben
Journal: Cancer Research (2009)

Resveratrol is a natural plant Nutraceutical that has medicinal effects in the prevention of cancer, aging and other maladies. Our laboratory is interested in determining the mechanism of action of Resveratrol to determine if Resveratrol can also be used in cancer therapy. In our original studies, ovarian cancer cells treated with Resveratrol arrested in S phase with DNA damage checkpoint foci as detected by phosphorylated histone H2AX staining. The entire ATM/ATR checkpoint pathway was activated resulting in direct phosphorylation of H2AX on chromatin and culminating in the inhibition of CDK (cyclin-dependent kinase) activity that drives the cell cycle. Resveratrol is not just activating the checkpoint pathway but also induces DSB (double-stranded DNA breaks) as detected by the \#8220;comet\#8221; assay. In contrast, normal HFF (human foreskin fibroblasts) were unaffected in all assays. We hypothesize that Resveratrol like radiation damages DNA, which is not repaired efficiently in cancer cells resulting in checkpoint activation and cell cycle arrest. Resveratrol was also found to arrest many different cancer cell lines (Head and Neck, Breast and Ovarian) independently of p53. Resveratrol and a number of similar polyphenols are regulators of the Sirtuin (SIRT) family of protein deacetylases. Because five different polyphenols that can activate Sirtuins also activated the DNA damage checkpoint, both the anti-cancer and anti-aging effects of these plant polyphenols depend on Sirtuin protein deacetylation. Because Resveratrol acts similarly to radiation, Resveratol can be thought of as a non-toxic radiomimetic. In this regard, we propose that Resveratrol will sensitize tumors to the effects of radiotherapy without effecting normal cells or producing side effects. Head and Neck squamous cell carcinoma (HNSCC) is a good model to test the hypothesis because Radiation is used as a treatment for HNSCC but with limited success and with a myriad of side effects. Towards this end, we have found that Resveratrol synergizes with radiation in killing HNSCC cells in vitro at clinically relevant radiation doses. Our current plan includes expanding our in vitro results to in vivo animal xenografts and a clinical feasibility study of the effect of Resveratrol on radiation treatment of HNSCC patients.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3989.
COVID-19 and cancer: Strategic health promotion for indigenous Australians during a pandemic.
Authors: Carolyn Der Vartanian, Vivienne Milch, Gail Garvey, Cleola Anderiesz, Jane Salisbury, Candice-Brooke Woods, Melissa Austen, Rhona Wang, Dorothy Mary Kate Keefe
Journal: Journal of Clinical Oncology (2021)

e24028 Background: Given the impact of COVID-19 on Indigenous and ethnic minority populations observed globally, keeping COVID-19 out of vulnerable Aboriginal and Torres Strait Islander (Indigenous Australian) communities remains a priority. Compared to non-Indigenous Australians, Indigenous Australians experience disparities in cancer incidence and outcomes due to social disadvantage, increased cancer-related modifiable risk factors, poorer access to health services and lower participation in screening. During the pandemic, cancer-related investigations and treatment reduced significantly in Australia, leading to potential decreases in cancer diagnoses and consequences for future survival outcomes. Concerned about the risk of morbidity and mortality due to COVID-19 for Indigenous Australians, as well as worsening cancer outcomes, Cancer Australia undertook strategic health promotion initiatives, to inform and support optimal cancer care. Methods: In consultation with respected Indigenous colleagues to ensure cultural appropriateness of language and information, we published a dedicated webpage titled ‘ Cancer and COVID-19 – what it means for our Mob*’ with tailored information, advice, and links to key resources and support services for Indigenous Australians. We also released a video titled ‘ Act early for our Mob’s Health’, providing targeted, culturally appropriate, consumer-friendly information to encourage Indigenous Australians to see their doctor or Aboriginal Health Worker with symptoms that may be due to cancer. Results: The information hub has been well-received among the Indigenous Australian community, receiving over 3,200 visits, and the social media campaigns have received over 1.4 million impressions and 46,000 video views between mid-March 2020 to mid-February 2021. This campaign has supported proactivity among the Indigenous population in keeping their communities safe during the pandemic, maintaining a population rate of COVID-19 of less than one percent of all confirmed cases in Australia. Conclusions: Culturally appropriate information and resources developed through the process of co-design can help to influence positive health behaviour change in Indigenous populations. We predict that our strategic, multi-channel health promotion campaign is contributing to keeping the Indigenous Australian community safe and informed during the pandemic, with additional work needed to monitor cancer rates and outcomes and address the ongoing information needs of the community. *Mob is a colloquial term to identify a group of Indigenous Australians associated with a family or community from a certain place.
Subgroup analysis by Ki-67 and baseline CgA of the randomized, placebo-controlled phase 3 study of surufatinib in advanced well-differentiated pancreatic neuroendocrine tumors (SANET-p).
Authors: Xianjun Yu, Jianming Xu, Lin Shen, Chunmei Bai, Jie Li, Zhiwei Zhou, Zhiping Li, Enxiao LI, Xianglin Yuan, Yihebali Chi, Yongmei Yin, Wenhui Lou, Nong Xu, Yuxian Bai, Tao Zhang, Dianrong Xiu, Xiuwen Wang, Sha Guan, Qian Xu, Weiguo Su
Journal: Journal of Clinical Oncology (2021)

4111 Background: In the phase 3 SANET-p trial (NCT02589821), surufatinib significantly increased progression-free survival (PFS) compared with placebo in patients with progressive, well-differentiated (grade 1 or 2), advanced pancreatic neuroendocrine tumors (NETs). Here we report the relationship of Ki-67 and baseline Chromogranin A (CgA) on efficacy outcomes. Methods: A total of 172 patients with advanced pancreatic NETs were randomized to surufatinib or placebo in a 2:1 ratio. Investigator-assessed PFS and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 were used for the analysis. The post-hoc subgroup analyses were performed on Ki-67 subcategory: &lt; 5% (n = 40 vs 21), 5-10% (n = 57 vs 31), &gt; 10% (n = 16 vs 7), and baseline CgA subcategory: ≤ 2 times of upper limit of normal (ULN) (n = 59 vs 31), &gt; 2 × ULN (n = 44 vs 24). Results: In the intent-to-treat population, surufatinib was superior to placebo, median PFS (mPFS) of 10.9 vs 3.7 months (mo) ( p = 0.0011), with a stratified hazard ratio (HR) of 0.491 (95% confidence interval [CI]: 0.319, 0.755). mPFS was statistically significantly longer in the surufatinib arm versus that in the placebo arm in subgroups of Ki-67 5-10% (11.0 vs 3.7 mo, HR = 0.33, p= 0.0002), Ki-67 &gt; 10% (11.1 vs 2.8 mo, HR = 0.04, p = 0.0003) and CgA &gt; 2 × ULN (11.0 vs 3.7 mo, HR = 0.36, p = 0.0036). There was numerical PFS improvement with surufatinib compared to placebo in subgroup of Ki-67 &lt; 5% (9.3 vs 5.6 mo, HR = 0.91, p = 0.8015) and CgA ≤ 2 × ULN (9.4 vs 3.7 mo, HR = 0.61, p = 0.0809). ORRs in the subgroups of Ki-67 &lt; 5%, 5-10%, and &gt; 10% with surufatinib were 15.8%, 24.0% and 12.5% respectively. There was only one partial response in the placebo arm (with Ki-67 &lt; 5%). ORRs in the subgroups of CgA ≤ 2 × ULN and &gt; 2 × ULN with surufatinib were 18.9% and 21.4%, while also only one partial response in the placebo arm with CgA ≤ 2 × ULN. Conclusions: Surufatinib showed statistically significant and clinically meaningful improvement in PFS compared to placebo in patients with advanced, progressive, well-differentiated pancreatic NETs. From this exploratory analysis, surufatinib demonstrated benefit irrespective of Ki-67 expression levels or baseline CgA. Clinical trial information: NCT02589821.
Abstract 13289: Increased Advanced Glycation End Products are a Risk Factor of Epicardial Adipose Tissue Thickness
Authors: Shusuke Yagi, Masataka Sata
Journal: Circulation (2019)

Introduction: Epicardial adipose tissue (EAT) surrounding the coronary artery is known as a risk factor of coronary artery disease (CAD). EAT is thicker in patients with type II diabetes (T2DM) com...
Is chimeric antigen receptor T cell (CART) a destination procedure? Lower socioeconomic class who live farther from center have less access to CART.
Authors: Nausheen Ahmed, Ernie Shippey, Crissy Kus, Allison Appenfeller, Marc Steven Hoffmann, Aung M. Tun, Siddhartha Ganguly, Leyla Shune, Clint Devine, Rajat Bansal, Sunil H. Abhyankar, Muhammad Umair Mushtaq, Joseph McGuirk
Journal: Journal of Clinical Oncology (2021)

e18562 Background: Axicabtagene ciloleucel and tisagenlecleucel are commercially available CD19 chimeric antigen receptor T-cell (CART) therapies for B cell malignancies. Manufacturing pharmaceutical companies require patients to stay within 2 hours of the center for 4 weeks post infusion. Most centers require local lodging for that period if residence is over 30 minutes away. Financial burden may limit access. We therefore hypothesized that those who were likely to receive CART therapies were from higher income neighborhoods or lived closer to the facility. Methods: Since most patients get admitted for CART infusion, we used the Vizient CDB database for CART infusion admissions as well as other admissions. Patients over the age of 18 yrs who got commercially available CART between 2018 to 2020 were included. Distance was calculated in miles from patient zip code to treating center. Using census data, lower income neighborhoods (less than $40,000 median household income) were flagged. Results: 81 centers administered CART. We calculated the distance in miles between the patient and the center for both CART admissions as well as for all-cause inpatient admissions. Most admissions (81.2% all-cause vs 78.6% CART) were from neighborhoods with median income &gt; $40,000. Most of the low-income admissions were from neighborhoods &lt;10 miles (13.3% all admissions vs 15.7% CART). 80.6% of all CART patients came from neighborhoods over 10 miles, with 38.2% living over 60 miles away, while only 15.4% all-cause admissions were from &gt; 60 miles. (p&lt;.0001) While 74.9% of higher income CART patients lived beyond 10 miles from center, only 5.7% CART patients lived beyond 10 miles. Results summarized in Table. Conclusions: Most CART patients lived over 10 miles from the center, however less than 10% of them were from lower income neighborhoods. Neighborhood location relative to center and household income influence access and need to be addressed.[Table: see text]