tbuckley/cabot-search huggingface dataset:
Demographic differences of colorectal cancer in the community and academic setting in patients over the age of 75 compared to those aged 50 to 75.
Authors: Kafayat Adebukola Busari, Renee Williams, Jamie Huston, Oliver Stewart, Darrel Gachette, Kenneth Lee Meredith
Journal: Journal of Clinical Oncology (2021)

e15594 Background: The age of life expectancy in the United States is 78.9 years of age and continues to increase with the help of public health initiatives along with scientific and technological breakthroughs in medicine. However, colorectal cancer screening guidelines for those over age 75 are individualized and not recommended in those over 85. We aimed to investigate the demographic differences of colorectal cancer by sex and race in patients aged 75 vs those aged 50-75, in the community and academic practice. Methods: Data were analyzed from the National Cancer Database between 2010-2014. Results were divided into two categories (50-75 year old, &gt;75 year old) and included number of patients, sex and race. Patient characteristics were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Data was further analyzed comparing sex and race using chi-square analysis. Results: 167, 059 patients were included in the analysis. 49,551 cases identified in the academic practice and 117, 508 in the community practice. In the academic practice, group A (age 50-75), 57.3% (20,810) were male vs. 42.7% (15,488) female. In community practice, group A, 56.5% (43, 915) were male vs 43.5% (33, 742) female (p-value &lt;0.05). Conversely, in the academic practice-group B (age &gt;75), 46.2% (6127) were male vs 53.8% (7126) female. In the community practice-group B, 55.3% (22,027) were female vs 44.7% (17,824) male; (p-value &lt;0.05).For Black patients, decline in cases is seen by age. In academic practice, 16.5% of cases were aged 50-75 vs. 11.9% over age 75. In community practice; 11.5% were aged 50-75 vs. 6.5%, p&lt;0.05). Comparatively there was an increase in cases in White patients by age diagnosed in academic and community practice; 77.5% vs 84.2 in 50-75 and 84.8 vs. 90.9% in &gt;75, respectively (p&lt;0.05). Conclusions: Women age &gt;75 comprised a statistically significant greater proportion of colorectal cancer cases compared to men age &gt;75 in both the community and academic setting. Contrary to established reports detailing higher incidence rates in males aged 50-75. Furthermore, there is an increase in cases with age in White patients in comparison with a decrease in cases in Black patients. These findings may suggest the need for a more universal and less individualized approach for individuals over age 75.
Healthcare utilization and outcomes in cervical cancer with and without HIV: National inpatient sample analysis.
Authors: Vedavyas Gannamani, Muhammad Junaid Tariq, Syed Ali Amir Sherazi, Muhammad Usman Almani, Niveditha Mudegowdra, Muhammad Usman, Shweta Gupta
Journal: Journal of Clinical Oncology (2021)

e17522 Background: Cervical cancer (CC) is an AIDS-defining malignancy and is the most common cancer in women with HIV who have a six times higher risk of developing CC than women without HIV. Compared to non-HIV-CC, HIV-CC has a reported 2-fold higher mortality. We attempted to evaluate the characteristics, outcomes and healthcare utilization of patients with CC with and without HIV from a national sample. Methods: We identified all patients of CC with and without HIV between 2016 – 2018 from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes (SO) included rates of sepsis, septic shock, pain, acute kidney injury, urinary tract infection, hydronephrosis, nephrostomy, anemia, and protein energy malnutrition (PEM). Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 755 admissions with HIV-CC and 71, 690 with non-HIV-CC were identified. Patients of HIV-CC were more likely to be younger (Mean age: 48.7 vs 53.4, p &lt; 0.001), African American (62.8% vs 18.4%, p &lt; 0.001), have Medicaid (52.3% vs 34.5%, p &lt; 0.001), admitted to a teaching hospital (90.7% vs 78.7%, p &lt; 0.01), live in lowest income ZIP codes (62.2% vs 36.2%, p &lt; 0.01) and in Northeast region of USA (30.5% vs 17.3%, p &lt; 0.01). HIV-CC had significantly higher rates of chronic kidney disease (CKD) and hemodialysis (HD) (p &lt; 0.05), lower rates of hypertension (p &lt; 0.05) with other comorbidities being similar between groups. The overall adjusted all cause mortality was significantly lower in HIV-CC (aOR = 0.15, CI 0.05-0.39, p &lt; 0.001) but mean LOS (8.3 vs 5.6 days, p &lt; 0.01) and THC ($86, 171 vs $63, 138, p &lt; 0.01) was significantly higher than non-HIV-CC. The rates of anemia (70.2% vs 52.8%) and PEM (27.8% vs 20.5%) were significantly higher (p &lt; 0.05) in HIV-CC while other SOs were non-significant. Conclusions: HIV-CC inpatients were younger, minorities from low income zip codes and, unlike historic data, had significantly lower mortality compared to non-HIV-CC. Despite lower mortality, LOS and THC were significantly higher in HIV-CC, amounting to over $17 million in 3 years. It may be related to a higher burden of CKD and HD, however more studies are needed to clarify our findings and identify causes of increased healthcare utilization in this group to save costs.
Discovery of HBW-3-20, the first potent reversible inhibitor of Bruton’s tyrosine kinase (BTK) with high brain exposure.
Authors: Ning Lee, Yingfu Li, Chester Yuan, Guanfeng Liu, Chunchao Yue
Journal: Journal of Clinical Oncology (2021)

e15068 Background: It has been an on-demand task to develop a BTK inhibitor of significant brain exposure, a critical property for extending its usages to treat Primary Central Nervous System Lymphoma (PCNSL) and autoimmune disorders. PCNSL is an aggressive extra nodal non-Hodgkin lymphoma that exclusively invades the central nervous system (CNS). Tirabrutinib, an irreversible BTK inhibitor with limited brain exposure, is the first BTK inhibitor approved for the treatment of recurrent or refractory primary central nervous system lymphoma recently. PRN2246 is another irreversible BTK inhibitor claimed to be of brain exposure, and is currently in clinical trials for the treatment of multiple sclerosis. Methods: New reversible BTK inhibitors were designed, synthesized and tested for enzymatic activities against wild-type and C481S-mutated BTK. Highly active compounds were confirmed for growth effects in diffuse large B-cell lymphoma derived TMD8 cells. Their microsomal stability and ADME properties were also assessed. Potent and bioavailable compounds were further measured for brain exposures in rats. Results: HBW-3-20 has excellent potency against both wild-type and C481S-mutated BTK, with IC 50 of 2.5 and 3.8 nM, respectively. Its TMD8 cellular potency is 72 nM. In a head-to-head direct comparison of brain exposure experiment, HBW-3-20, tirabrutinib and PRN2246 were all dosed at 10mg/kg orally. The brain and plasma concentration were measured after 1 hour and the data are shown in the table below. The brain to plasma ratio for HBW-3-20, tirabrutinib and PRN2246 are 58%, 11.8% and 4.2% respectively. Our results show that HBW-3-20 has much greater brain permeability than tirabrutinib or PRN2246 in rats. Conclusions: HBW-3-20 is the first potent reversible BTK inhibitor that shows promisingly high brain permeability. HBW-3-20 provides a very valuable clinical candidate for treating B-cell malignancies in brain and autoimmune disorders![Table: see text]
Consensus molecular subtypes and <i>RAS</i> status as biomarker of treatment intensity with fluoropyrimidine, bevacizumab, and irinotecan in metastatic colorectal cancer (XELAVIRI, AIO KRK 0110).
Authors: Arndt Stahler, Volker Heinemann, Veronika Schuster, Annabel Helga Sophie Alig, Laura Elisabeth Fischer, Lena Weiss, Kathrin Heinrich, Annika Kurreck, Ivan Jelas, Jobst C. von Einem, Clemens Giessen-Jung, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Thomas Decker, Jens Neumann, Thomas Kirchner, Andreas Jung, Joerg Kumbrink, Sebastian Stintzing, Dominik Paul Modest
Journal: Journal of Clinical Oncology (2021)

3552 Background: Prognostic biomarkers beside RAS/BRAF status are necessary to identify metastatic colorectal cancer (mCRC) patients who benefit from combined (COMB) versus sequential (SEQ) treatment with fluoropyrimidine, bevacizumab and irinotecan (randomized phase III XELAVIRI trial). Methods: mRNA was extracted from formalin-fixed paraffin embedded (FFPE) tumor tissue of 337 patients, gene expression was measured by the Nanostring PanCancer Progression Panel. Consensus molecular subtypes (CMS) classification was re-derived using a multinomial regression model. Data of Guinney et al. (Nat. Med. 2015. 21:1350-6) and FIRE-3 served as training and validation set. RAS/BRAF MUT were assessed by pyrosequencing. Median overall (OS) and progression free survival (PFS), hazard ratios (HR) and 95% confidence interval (CI) were estimated by Kaplan-Meier method and univariate Cox regression. Results: The multinomial regression model employed in the present analysis correctly predicted CMS labels in 98.3 % of the original Guinney- and 100.0 % of FIRE-3 population. In XELAVIRI, CMS subgroups were predicted as follows: CMS1: n = 62 (18.4 %); CMS2: n = 174 (51.6 %); CMS3: n = 9 (2.7 %); CMS4: n = 92 (27.3 %). A general prognostic impact of CMS was not observed when all patients were analysed. In RAS/BRAF WT mCRC patients, substantial benefit of COMB versus SEQ treatment was shown for OS and PFS in CMS2 and CMS4, but not in CMS1. Conversely, OS was significantly longer for COMB treatment in patients with RAS MUT and CMS1 mCRC, while SEQ treatment was not inferior in RAS MUT and CMS2 or CMS4 subgroups (see TABLE). Additional data for overall response rates, early tumor shrinkage and sidedness might be presented at the meeting. Conclusions: This retrospective analysis of XELAVIRI suggests that CMS may serve as biomarker that predicts response to initially combined versus less intensive sequential chemotherapy in patients with RAS/BRAF WT mCRC.[Table: see text]
Rural health cancer care: A literature review.
Authors: Wade T. Swenson, Emily Westergard, Abigail Paige Swenson
Journal: Journal of Clinical Oncology (2021)

e18500 Background: A recent review of the medical literature of rural health cancer care delivery has not been published. We conducted a preliminary review of the last twenty years of rural health cancer care delivery literature utilizing medical subject headings (MeSH) within the PubMed NCBI) database. Methods: Using PubMed MeSH Major Topic terms “rural population” and “cancer” we identified publications published from 2000 to 2020. We searched PubMed for publications that included the major topic MeSH terms “rural population” and “cancer”. We individually reviewed articles, confirmed the focus of the article, and subcategorized the articles. Results: We identified 580 publications which met the search criteria, the majority were focused on the United States (266), followed by China (56), Australia (54), and India (27). Among the publications focusing on the United States, 76 involved Appalachian States. Kentucky (18) and Georgia (10) were the states most frequently represented. Malignancies most commonly represented were: breast cancer (148), uterine/cervical (84), and colorectal cancers (68). The journals which published the most rural health cancer care delivery were The Journal of Rural Health (42), Asian Pacific Journal of Cancer Prevention (20), Cancer (14), Rural and Remote Health (13), Journal of Cancer Education (13), Australian Journal of Rural Health (12). Conclusions: The rural health cancer care literature in the last two decades focuses primarily on the United States, China, Australia, and India. Within the United States, the research focus is Appalachia. The majority of articles focus on breast cancer, uterine/cervical, and colorectal cancers. The journal which published the majority of rural health cancer care articles was the Journal of Rural Health.
Cell-free, quantitative mineralization measurements as a proxy to identify osteoinductive bone graft substitutes
Authors: Yassine Maazouz, Giacomo Chizzola, Nicola Döbelin, Marc Bohner
Journal: Biomaterials (2021)

Some synthetic bone graft substitutes (BGS) can trigger ectopic bone formation, which is the hallmark of osteoinduction and the most important prerequisite for the repair of large bone defects. Unfortunately, measuring or predicting BGS osteoinductive potential based on in vitro experiments is currently impossible. A recent study claimed that synthetic BGS can induce bone formation ectopically if they create a local homeostatic imbalance during their in vivo mineralization. This raised the hope that a simple cell free in vitro mineralization experiment would correlate with osteoinduction. The aim of the present study was therefore to assess the ability of a quantitative in vitro mineralization test to predict and rank the osteoinductive potential of BGS. Eight calcium phosphate BGS already tested ectopically in 9 different in vivo studies were used for that purpose. The experiment was able to identify materials that are reliably osteoinductive from those that are not, but was inaccurate in ranking the osteoinductive materials between each other. Chemical contaminants (Ca2+, Mg2+, H+, OH−, PO43−) present in some of the BGS affected the in vitro mineralization experiment results, but not in a direction that could explain the different rankings. In conclusion, this study suggests that an in vitro experiment can be used as a fast and reliable screening tool to identify osteoinductive BGS and underline the need to study ionic contaminants on calcium phosphate BGS.
Benefits of pembrolizumab in progressive radioactive iodine refractory thyroid cancer: Results of the AcSé Pembrolizumab Study from Unicancer.
Authors: Sophie Leboulleux, Yann Godbert, Nicolas Penel, Segolene Hescot, Christelle De La Fouchardiere, Marie Blonski, Livia Lamartina, Sophie Cousin, Christine Do Cao, Julien Hadoux, Clotilde Simon, Natalie Hoog Labouret, Sylvie Chevret, Christophe Massard
Journal: Journal of Clinical Oncology (2021)

6082 Background: AcSé Pembrolizumab is a Phase II, non-randomized parallel arm, open-label, multicentric study from Unicancer investigating the efficacy and safety of pembrolizumab monotherapy in different cohorts of patients with rare cancers (NCT03012620). Here we report the first results of pembrolizumab in the radioactive iodine refractory thyroid cancer cohort. Methods: Main inclusion criteria were progressive radioactive iodine refractory (RAIR) thyroid cancer (TC) resistant to standard treatment, age &gt; 18, ECOG PS≤1. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response (OR) rate according to RECIST v1.1 by investigator. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: 43 patients (21 female, mean age 64.8 years; range 40-86) with TC (27 patients with differentiated TC (DTC) [papillary: 7; follicular: 14: oncocytic: 5 poorly differentiated: 1] and 16 patients with anaplastic TC (ATC)) were included from September 2017 to December 2020. The median number of previous systemic treatment lines was 2 (range, 0-7) in DTC and 2.5 (range, 1-4) in ATC. The median number of pembrolizumab cycles was 4 (range, 1-35). The median follow-up was 5.9 months (range: 22 days-22.9 months) for DTC and 2.7 months (range: 3 days- 24.4 months) for anaplastic TC. For DTC the best tumor response was partial response (PR) in 3 (11.1%) patients and stable disease (SD) in 5 (18.5%). Median duration of response was 2.5 months (range: 5 days-7.2 months). The median PFS was 2.6 months, the 6-month PFS was 16.9 %. The median OS was 12.7 months with a 6-month OS of 73.3%. For ATC the best tumor response was PR in 3 cases (18.8 %) and SD in 1 case (6.2 %). Median duration of response was 1.6 months (range: 2 days-7.2 months). The median PFS was 2.3 months, the 6-month PFS was 33.8 %. The median OS was 3.6 months with a 6-month OS of 32.9%. Treatment emergent adverse event included 9 Grade 1-2, 20 Grade 3 (3 being considered as related and 17 as not related) and 1 Grade 4 (sepsis, unrelated). Overall, the toxicity profile was similar to that observed in other cancers. Conclusions: The response rates observed under pembrolizumab is low in DTC and not negligible in ATC, but with a short duration of response. Clinical trial information: NCT03012620.
A pan-cancer analysis of MUC family genes as potential biomarkers for immune checkpoint therapy.
Authors: Yang Li, Qianqian Duan, Yuan Tan
Journal: Journal of Clinical Oncology (2021)

2598 Background: Mucin (MUC) is a family of high-molecular weight glycoproteins and increased mucin production occurs in many malignant tumors. Recent studies have found relationship between mutations of some MUC family genes and efficacy of immunotherapy. Here, we explored the associations of MUC family genes (MUC2, MUC3A, MUC4, MUC5B, MUC6, MUC12, MUC16, MUC17, MUC19) mutation with ICI response based on multidimensional data from multiple solid tumors. Methods: 15 solid tumor types of TCGA genomic data for 6138 patients was used to evaluate tumor mutational burden (TMB) differences between MUC family genes mutation group and wildtype group. TMB was calculated as the total count of nonsynonymous mutations in coding sequence. Neoantigens of 3039 samples across 11 solid tumor types were obtained from The Cancer Immunome Atlas. A pan-cancer immunotherapy cohort (Broad/Dana-Farber, Nat Genet 2018, N = 249) was used to explore the relationship between mutations of MUC family genes and its efficacy of immunotherapy. Results: The most common mutated MUC genes (frequency &gt; 5%) were MUC16 (25.3%), MUC17 (10.8%), MUC5B (10.5%), MUC4 (8.6%), and MUC2 (5.1%). The data between MUC mutation group and wild type group showed a significant difference (P &lt; 0.01) in TMB. Median TMB across fifteen tumors in MUC mutation group and wild type group is 7.04 mutations per Mb and 2.07 mutations per Mb, separately. The TNB between two group is also showed a significant difference (P &lt; 0.01). Median TNB across nine types tumor in MUC mutation group and wild type group is 121.5 neoantigens and 34.0 neoantigens, separately. A multivariable analysis across the pan-cancer cohort using Cox proportional-hazards regression demonstrated that KMT2C mutation was associated with better OS (hazard ratio, 0.66; 95%CI, 0.45-0.99; P = 0.042), adjusting for sex and cancer type. Conclusions: The results indicated that MUC family genes mutation was associated with a higher TMB and TNB. Analysis of immunotherapy cohort data showed MUC family was associated with better OS. These findings indicate that these genes mutation may serve as a predictive biomarker for ICI in solid tumor patients.
The prognostic value of tumor markers in patients (pts) with resectable gastric cancer (GC) receiving perioperative therapy in the CRITICS trial.
Authors: Astrid E. Slagter, Marieke A. Vollebergh, Irene A Caspers, Johanna W. van Sandick, Karolina Sikorska, Pehr A. Lind, Marianne Nordsmark, Hein Putter, Jeffrey P.B.M. Braak, Elma Meershoek – Klein Kranenbarg, Cornelis J.H. Van De Velde, Edwin PM Jansen, Annemieke Cats, Hanneke W.M. Van Laarhoven, Nicole C.T. van Grieken, Marcel Verheij
Journal: Journal of Clinical Oncology (2021)

4024 Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are well-known tumor markers. Most studies on CEA and CA 19-9 in pts with GC were performed in Asia, and/or in the metastatic setting. The aim of this study was to investigate the prognostic value of blood derived laboratory parameters in a cohort of European pts with resectable non-metastatic GC. Methods: In the CRITICS trial, 788 pts with resectable GC underwent perioperative therapy (preoperative chemotherapy plus either postoperative chemotherapy or postoperative chemoradiotherapy). Blood levels of CEA, CA 19-9, alkaline phosphatase (AP), creatinine, neutrophils, hemoglobin (Hb) and lactate dehydrogenase (LDH) were determined prior to treatment. Data for these variables were available for at least 89% of the pts. Factors significant on univariable cox regression analysis were further explored in multivariable analysis. Probabilities to undergo potentially curative surgery was investigated for factors significant on multivariable analysis. The relationship between tumor markers and the presence of circulating tumor DNA (ctDNA) was explored in 50 pts with available ctDNA data. Results: CEA and CA 19-9 were identified as independent prognostic factors for survival (Table). Probabilities to undergo potentially curative surgery were 86%, 77% and 60% for pts with no elevated tumor makers versus those with elevated CEA or elevated CA 19-9 versus those with both tumor markers elevated, respectively (p&lt;0.001). No relationship was found between elevated tumor marker(s) and the presence of ctDNA neither pretreatment nor preoperatively. Conclusions: Pretreatment blood levels of CEA and CA 19-9 were identified as prognostic factors for overall survival in a large cohort of European GC pts with potentially curable disease. These factors may guide treatment choices at an early phase and should be included in future trials to determine their role in clinical decision making.[Table: see text]