bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic landscape of Chinese patients with upper tract urothelial carcinoma.
Authors: Jin Shengming , Wei Yu , Wu Junlong , Gu Chengyuan , Gao Wenqi , Li Bing , Zhu Yao , Ye Dingwei 
Published: June 2021

e16583 Background: Upper tract urothelial carcinoma (UTUC) is known to have a distinct aggressive clinical phenotype and its genomic characterization is poorly understood, especially in Asian population. In this study, we aimed to characterize the genomic landscape of Chinese UTUC patients and explore the clinical relevance, which is the largest cohort of UTUC to date. Methods: Overall, 122 Chinese patients with UTUC were enrolled. Tumor and germline DNA from patients were analyzed using a targeted next-generation sequencing assay to identify somatic mutations in 520 cancer associated genes. Mutations like deletion, amplification and gene fusion were included. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also evaluated. The frequency of genomic alterations in patients with UTUC was compared with that of the Western counterpart from previous studies. Results: In total, 13 low-grade and 109 high-grade UTUC patients were included in this study. The most frequent genomic alterations were identified in genes like TERT (50.0%; 61.5% low-grade vs 48.6% high-grade), KMT2D (48.4%; 61.5% vs 46.8%), FGFR3 (41.0%; 69.2% vs 37.6%), TP53 (37.7%; 7.7% vs 41.3%), CDKN2A (22.1%; 23.1% vs 22.0%), KDM6A (20.5%; 15.4% vs 21.1%) with different mutation frequencies in the two subgroups of patients. Despite the overall similarity (including FGFR3, ARID1A and CDKN2A), the comparison between our cohort and the two Western UTUC cohorts (n = 119, 24 low-grade and 95 high-grade) revealed significant differences in mutation frequencies of KMT2D (48.4% vs 36.1%), TERT (50.0% vs 26.9%), TP53 (37.7% vs 21.9%) and KDM6A (20.5% vs 32.8%) . Chi-square analysis revealed that patients with history of other cancers (4/17 vs. 3/105, P = 0.001) were more likely to have a MSI-high status. In addition, females (9/44 vs. 6/78, P = 0.039) and patients with cancer history (6/17 vs. 9/105, P = 0.002) were more likely to have high TMB (≥20 mutations/Mb; median: 6.48 mutations/Mb). At last, the frequency of germline P/LP variants were also similar but different in the spectrum between our cohort and the Western UTUC population. Differences in mutation frequency of APC (0 vs 2.6%), BRAC2 (2.6% vs 0.9%), CHEK2 (0.3% vs 1.8%), MSH2 (2.6% vs 5.3%) and MSH6 (0 vs 1.8%) were significant. Conclusions: This study revealed that Chinese UTUC patients had a similar frequency of genomic alterations with western patients. However, there were significant differences in the prevalence of several mutated genes including KMT2D, TERT, TP53 and KDM6A, suggesting the ethnicity differences between the two populations. Our findings laid the foundation of a deeper understanding of UTUC biology and will provide potential targets for the development of precision therapies in UTUC.
Combination ozone therapy as an effective method of radiomodification in chemoradiation treatment of patients with cervical cancer.
Authors: Rodionova Olga G. , Gusareva Marina A. , Sheiko Elena A. , Voshedskiy Vitaliy I. , Sakun Pavel G. , Vasilieva Ekaterina O. , Karnaukhova Elena A. , Solntseva Anna A. , Kosheleva Natalia G , Krokhmal Yulia N. , Pustovalova Alla V. , Chalabova Tatiana G. , Dontsov Vladimir A. , Kabanov Sergey N. , Vlasov Stanislav G. 
Published: June 2021

e17515 Background: The purpose of the study was to evaluate advantages of combination ozone therapy as an effective factor of radiomodification and radioprotection in the treatment of patients with cervical cancer. Methods: The study included 20 patients with stage IIIb cervical cancer T3бNхM0, the mean age 52 years. Controls (n = 10) received standard chemoradiation therapy; the main group (n = 10) received combination ozone therapy in addition to chemoradiation therapy. Systemic ozone therapy involved intravenous administration of 250 ml ozonized solution of 0.9% sodium chloride, 15 sessions during external beam radiotherapy. Local ozone therapy involved 15-minute instillations into the vagina during brachytherapy. All patients received standard chemoradiation therapy, total irradiation dose to the primary focus 80 Gy, plus weekly cisplatin 40 mg/m2. Results: In the main group, pain and discomfort in the lower abdomen were managed in 20% patients by the 5th session of ozone therapy; 30% - on the 10th day; in 50% - on the 14th day. In the control group, such symptoms in 40% of patients were reduced after 20 days. The main group showed a more rapid regression of tumor infiltration, disappearance of purulent discharge, relief of intoxication syndrome. Manifestations of gastrointestinal toxicity were observed in 10% of the main group and in 100% controls; leukopenia developed in 7 patients in the control group and was not registered in the main group. MRI showed complete clinical regression in 90% in the main group and in 65% in the control group. The treatment was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Combination ozone therapy causes a more pronounced antitumor effect, and its radioprotective effects significantly reduce the severity of chemotherapy-induced disorders. It does not aggravate concomitant pathology and shortens the treatment period.
Healthcare utilization and outcomes in cervical cancer with and without HIV: National inpatient sample analysis.
Authors: Gannamani Vedavyas , Tariq Muhammad Junaid , Sherazi Syed Ali Amir , Almani Muhammad Usman , Mudegowdra Niveditha , Usman Muhammad , Gupta Shweta 
Published: June 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 < 0.001), African American (62.8% vs 18.4%, p < 0.001), have Medicaid (52.3% vs 34.5%, p < 0.001), admitted to a teaching hospital (90.7% vs 78.7%, p < 0.01), live in lowest income ZIP codes (62.2% vs 36.2%, p < 0.01) and in Northeast region of USA (30.5% vs 17.3%, p < 0.01). HIV-CC had significantly higher rates of chronic kidney disease (CKD) and hemodialysis (HD) (p < 0.05), lower rates of hypertension (p < 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 < 0.001) but mean LOS (8.3 vs 5.6 days, p < 0.01) and THC ($86, 171 vs $63, 138, p < 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 < 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.
Genomic characteristics of endometrial cancer in China.
Authors: Zheng Hong , Cui Lina , Zhang Bei , Zhao Xiaochen 
Published: June 2021

e17569 Background: Molecular classification of endometrial cancer has been applied in patient stratification and treatment strategy. Although the Cancer Genome Atlas project and other genomic studies have established comprehensive molecular classification, its genomic characteristics in Chinese endometrial cancer remain unclear. Methods: Tumor tissue and matched white blood cells from 316 patients with endometrial cancer underwent next-generation sequencing (NGS), which targeted the whole coding region of 733 or 381 genes. Endometrial cancer was classified into four subtypes according to genomic characteristics: polymerase (POLE) ultramutated, microsatellite instability (MSI), TP53 wild type (TP53wt), and TP53 mutant (TP53mut). Tumor mutation burden (TMB) was calculated based on the number of somatic single nucleotide variants and indels in examined coding regions. Deleterious or suspected deleterious genes were included for analysis. Genomic instability was also evaluated with Homologous Recombination Deficiency (HRD) score by over 10, 000 single-nucleotide polymorphisms distributed across human genome. HRD algorithm combined loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST). Results: The 316 endometrial cancer patients were divided into four subtypes: POLE ultramutated (16, 5.06%), MSI tumors (70, 22.2%), TP53wt (131, 41.5%), and TP53mut (99, 31.3%). Median TMB was 26.5 mut/Mb in overall cohort and POLE ultramutated subtype possessed the highest TMB (181 mut/Mb), followed by MSI (54.1 mut/Mb), TP53mut (7.11 mut/Mb) and TP53wt (6.61 mut/Mb) subtypes. POLE, PTEN, LRP1B, BRCA2 and ATRX were the top frequently mutated genes in POLE ultramutated subtype, which mutation rate are more that 80%. The most frequent mutations were detected in ARID1A, PTEN, PIK3CA in MSI subtype, TP53, PIK3CA, PTEN in TP53mut subtype, and PTEN, PIK3CA, ARID1A in TP53wt subtype. HRD score was significantly higher in TP53mut subtype, followed by TP53wt, MSI and POLE ultramutated subtype (median HRD score, 21.7, 6.15, 3.65 and 0; P < 0.001). Conclusions: Our study revealed the heterogeneous genomic characteristics of four molecular subtypes in Chinese endometrial cancer. POLE ultramutated and MSI subtypes display higher TMB. TP53mut subtype showed genome features of HRD and would likely benefit from HRD-targeted therapy.
Radiomic features in recurrent/metastatic platinum refractory head and neck squamous cell carcinoma treated with immunotherapy.
Authors: Anile Giuseppe , Bettinelli Andrea , Paiusco Marta , De Conti Giorgio , Gottardi Chiara , Conte Pierfranco , Ghi Maria Grazia 
Published: June 2021

e18000 Background: Radiomics is the computerized extraction of quantitative features from medical images, beyond the level of detail accessible to an unaided human eye. Several studies on radiomic analysis have been carried out to identify predictive, prognostic and diagnostic biomarkers for diverse tumor types including HNSCC. Radiomic features proved to be effective in predicting outcomes in patients with locally advanced HNSCC. The aim of the present study was to dentify predictive and prognostic radiomic features in platinum-refractory HNSCC patients with recurrent and/or metastatic (R/M) disease treated with anti PD-1 monotherapy. Methods: We retrospectively reviewed the data of 38 patients treated with Nivolumab at our Institution between January 2018 and March 2020. Nasopharyngeal carcinomas were not eligible. CT radiomic textural features were extracted from regions of interests (ROIs) manually delineated around tumor volumes. Minimum Redundancy Maximum Relevance (mRMR) algorithm was the method of choice to rank radiomic features based on three outcomes: overall response rate (ORR); disease progression (PD) and overall survival (OS). Logistic regression was employed to build predictive/prognostic models. Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) was chosen as the metric to assess model performances. Results: Data from 29 out of 38 patients were ultimately analyzed. Nine patients were excluded due to nasopharynx as primary tumor site and/or inadequate CT scan imaging. A total of 57 ROIs were extracted and analyzed. We obtained 9 models: 3 radiomic models, 3 clinical models and 3 combined models (radiomic plus clinical) for each outcome of interest (ORR, PD, OS). In the radiomic models 2 features were identified as predictor for ORR (AUC 0.69), 1 radiomic feature was predictive for PD (AUC 0.83) and 1 predictive for OS (AUC 0.72). In the clinical models, 3 clinical characteristics were identified for both ORR (AUC 0.91) and PD (AUC 0.73) and 2 clinical features were found to be predictive for OS (AUC 0.91). The combined model identified 3 features (2 radiomics and 1 clinical) predictive for ORR (AUC 0.76). No clinical characteristics were found in the combined model for PD. No radiomics features have been shown to be related to OS. Conclusions: This is an explorative study to test the power of radiomics and the potential value of combining radiomics and clinical data as a prognostic and predictive instrument. In this small sample size, the quantitative analysis of CT images seems to be an interesting tool which has to be further explored as predictor of outcome in a larger series of patients.[Table: see text]
Development and validation of an unfolded protein response-related gene signature to predict overall survival in HNSCC.
Authors: Chen Jun , Zhang Bei 
Published: June 2021

e18033 Background: Genomic expression profiles have enabled the classification of head and neck squamous cell carcinoma (HNSCC) into molecular sub-types and provide prognostic information, which have implications for the personalized treatment of HNSCC beyond clinical and pathological features. Methods: Gene-expression profiling was identified in TCGA- HNSCC (n = 492) and validated with the Gene Expression Ominibus (GEO) dataset(n = 270) for which RNA sequencing data and clinical covariates were available. A single-sample gene set enrichment analysis (ssGSEA) algorithm were used to quantified the levels of various hallmarks of cancer. And LASSO Cox regression model was used to screen robust prognostic biomarkers to identify the best set of survival-associated gene signatures in HNSCC. Statistical analyses were performed using R version 3.4.4. Results: We identified unfolded protein response as the primary risk factor for survival（cox coefficient = 17.4 [8.4-26.3], P < 0.001）among various hallmarks of cancer in TCGA- HNSCC. And unfolded protein response ssGESA scores were significantly elevated in patients who died during follow up (P = 0.009). Kaplan-Meier analysis showed that patients with low ssGSEA scores of unfolded protein response exhibited better OS (HR = 0.69, P = 0.008). And we established an unfolded protein response-related gene signature based on lasso cox. We then apply the unfolded protein response -related gene signature to classify patients into the high risk group and the low risk group with the cutoff of 0.18. Adjusted for stage，age，gender, our signature was an independent risk factor for overall survival in TCGA cohorts (HR = 0.39 [0.28-0.53],P = < 0.001). In external independent cohorts, similar results were observed. In the validation cohort GEO65858, the patients with high unfolded protein response score showed longer survival (HR = 0.62 [0.38-1.0], P = 0.049). And adjusted for stage，age，HPV state, the multivariate cox regression analysis showed that unfolded protein response-related gene signature exhibited an independent risk prediction for overall survival in 270 patients with HNSCC (HR = 0.57 [0.35-0.94], P = 0.026). Conclusions: By analyzing the gene-expression data with bioinformation approach, we developed and validated a risk prediction model with unfolded protein response -related expression scores in HNSCC, which have the potential to identify patients who could have better overall survival.
Supportive care services (SCS) during curative-intent treatment with chemoradiation for patients with locally advanced head and neck cancer (HNC).
Authors: Harris Ethan , Kacew Alec , Sreedhar Siva , Shergill Ardaman 
Published: June 2021

e18041 Background: SCS assist in managing symptoms and outcomes for patients in palliative care settings. But impact of services in curative intent settings is not well defined. Here we evaluate this for head and neck cancer patients. Methods: Following IRB approval, we retrospectively reviewed charts of patients with HNC treated from 2014-2017 at the University of Illinois Hospital. Of 260 patient charts reviewed, 67 patients fit the study criteria, which included completing treatment with curative intent at University of Illinois Hospitals, not living at a skilled nursing facility, and follow-up of at least 3 months. Demographic data and treatment course data were collected. SCS included opioid use, tracheostomy use, G-tube use, prophylaxis for mucositis, speech and swallow f/u, nutritionist visits, social worker visits, and anti-emetic prophylaxis. Outcomes included number of hydration visits, number of ER visits, and number of days in the hospital. We tested the significance of correlations between continuous variables using Pearson correlation and the significance of difference in a continuous variable between two groups using the Wilcoxon ranked sum test. We used Cox proportional hazards model for analyses of overall survival (OS). Analyses were univariable. Results: 20 patients had oropharyngeal cancer. 47 had non-oropharyngeal disease. 57 patients received cisplatin and 10 patients received cetuximab, concurrently with radiation therapy. Median weight loss was 6.0kg during treatment. Highest potency opioid at end of treatment was not associated with outcomes. Among the full cohort, having a G-tube was associated with increased number of ER visits (median 1.5 vs. 0.0, p < 0.01), hospitalizations (median 2.0 vs. 0.0, p < 0.01), and number of days in the hospital (median 7.0 vs. 0.0, p < 0.01). Increased hydration appointments, meanwhile, did not predict outcomes. In subgroup analysis of patients who received G-tubes, ER visits before or after G-tube placement did not predict OS (HR 0.64, p = 0.56 for ER visits before G-tube placement, HR 1.06, p = 0.75 for ER visits after G-tube placement). Number of hydration visits after starting treatment for cetuximab vs cisplatin was significant (median 8 for cisplatin and 2 for cetuximab, p = 0.02). Conclusions: G-tube placement, even after placement, was associated with medical care needs during treatment, suggesting an unmet need for this patient population. Further studies are needed to determine how to best provide support for this vulnerable patient population.
Comparison of tongue cancer survival among White and Black cancer patients: An exploratory analysis of the SEER database.
Authors: Shah Jaffer , Shah Asghar , Shah Aarati , Aiash Hani 
Published: June 2021

e18053 Background: Despite the relatively rare incidence of tongue cancer in the United States, 2,830 people were estimated to have died from it in 2020. Research has indicated disparities in oral cancer screenings among minority and low-income patients. The aim of the present study is to characterize the incidence of tongue cancer across in the US population and to determine mediators of survival months. Methods: SEER 18 regions database (November 2019 submission) was queried to obtain data on tongue cancer incidence, patient demographics, and clinical variables for patients (n=51,622) from 2000-2017 using SEER*Stat 8.3.8. Data analysis were performed using R and RStudio version 4.02, and 1.3.1073, respectively. For comparison between groups, Chi-squared test for independence, Fisher’s exact test, and Wilcoxon signed-rank test were applied where applicable. Univariate and multivariate regression models characterized the relationship between survival months and sex, race, primary site, and additional patient characteristics. Results: Several significant group differences were determined in the incidence of tongue cancer. Patient sex was significantly associated (P<0.001), with survival months in White patients, with median survival months 33 (IQR 11,85) and 35 (IQR 12,82) for females and males respectively. Regression analysis found multiple patient level characteristics significantly mediating survival months. The odds ratio (OR) for reported patient race of Black were OR 0.78 (95% CI 0.68, 0.89; P<.001) and OR 0.75 (95% CI 0.66, 0.86; P<.001) for univariate and multivariate regression, respectively. Conclusions: The study indicates that health disparities vis-à-vis social determinants of health play a role in mediating differences in tongue cancer survival months for patients in the US. Further research should characterize and address persisting health inequities and potential solutions in oral cancer incidence and mortality.[Table: see text]
Social disparities in Southeastern Brazil and the burden of cervical cancer.
Authors: Aleixo Sabina B. , Pulido Jose Zago , Parmanhane Narelle , Sogame Luciana 
Published: June 2021

e18511 Background: Cervical cancer (CC) is the fourth most common malignancy in women worldwide and around 85% of the cases currently diagnosed are in underdeveloped countries. According to the National Cancer Institute of Brazil (INCA), in the year 2021, 16.590 new cases are expected with an estimated risk of 15.43 cases per 100,000 women and unfortunately numbers are not decreasing. Low socioeconomic status is been known to be associated with inferior cancer survival. Although Brazil’s publicly funded Unified Health System (SUS) increased access to health care, the universal access is still a problem. Brazil is a country of continental dimensions with widespread regional and social inequalities. The CC differs enormously by regions in the Brazilian country. Here, we use a population-based cancer registry to explore sociodemographic characteristics and CC in Southeastern Brazil. Methods: We collected retrospective data of patients with CC registered in the regional cancer reference center from the south of Espirito Santo (ES) the Hospital Evangélico de Cachoeiro de Itapemirim (HECI). We used the brazilian Health Information System - SISRHC from 2010 to 2017. Characteristics such as educational level (years of study), age, race, type of health insurance for treatment (SUS or private) and disease stage at diagnosis were recorded. Results: Among 3272 women diagnosed with cancer in the period analyzed, 286 had a diagnosis of CC.The educational level of 44,61% was less than 9 years, 16,43% between 10 and 12 years and 3,15% more than 12 years (36,01% without information).Mean age at diagnosis was 49 years, and 50 % were younger than 50 years. As for race, 50% of the women self-declared as non-white and 40,91% as white (9,09% without information), and 89,9% were treated by SUS and 10,1% treated by private health system. The distribution of CC stages at diagnosis was 0 (13,99%), I (15,03%), II (23,08%), III (18,53%) and IV (3,5%). Stage status was missing for 35,87% of CC cases. Conclusions: The majority of the women in the study where non-white, had low education level , used public health system (SUS) for treatment and had advanced disease. We also found that Brazilian SISRHC needs more attention to be a reliable cancer source data. These findings reinforce that social determinants affects access to diagnosis and treatment of CC patients in Southeastern Brazil. Future health awareness and preventive interventions must target less-educated communities to reduce delays in seeking medical care for cancer.