bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathologic analysis of MMR gene mutations and uterine adenocarcinomas: An updated population-based study.
Authors: Wang Aifen , Holloway Robert W. , Yang Jinsong , Pei Zhe , Sun Yan , Zhao Yingyan
Published: May 2020

e18100

Background: Endometrial carcinoma frequently harbors genetic alterations in genes encoding mismatch repair (MMR) enzymes, a finding which has important implications for adjuvant therapy. The aim of this study is to determine an optimal screening strategy to detect MMR mutations for each histologic subtype of endometrial carcinoma (EC). Methods: We performed a comparative analysis of the demographic, clinical, pathologic, and molecular data, including MLH1, MLH3, PMS1, PMS2, MSH2, MSH3, MSH6, and EPCAM, for 562 patients from The Cancer Genome Atlas database (TCGA), stratified by tumor histologic subtype. Results: Molecular data was available for 562 patients, of which 162 (28.8%) had tumors that were positive for MMR mutations. We did not separate somatic and germline mutation. Of these tumors, the penetrate rate of FIGO grade 3 endometrioid endometrial carcinoma (EEC G3) (84/184, 45.7%) was significantly higher than the one of uterine serous carcinoma (USC) (35/156, 22.4%) ( p < 0.001), grade 2 (EEC G2) (26/129, 20.2%) ( p < 0.001), and grade 1 (EEC G1) (17/93, 18.3%) ( p < 0.001). Of EEC G3 tumors, patients with MMR gene mutations were significantly older ( p = 0.024) or had lower BMI's than MMR mutation noncarriers ( p = 0.028). Of 562 endometrial carcinomas, alterations in MSH2 (n = 55), MSH6 (n = 54), MSH3 (n = 50) were the most frequent mutations. There were no differences in overall survival and progression-free interval between MMR mutation carriers and nonmutation carriers (p > 0.05) except that PFI with MMR gene mutation was higher than with MMR proficiency in EEC G3 ( p = 0.014). Conclusions: EEC G3 harbored the most MMR mutations among EC. EEC G3 and USC could be more considered to screen MMR mutation due to more MMR mutations occurred in EEC G3 and USC than did among EEC G2 and EEC G1. Besides MLH1, MSH2, MSH6, PMS2 and EPCAM mutation , MLH3, MSH3, PMS1 mutation could be screened in patients with newly diagnosed endometrial carcinoma. [Table: see text]
Validation of secreted protein OASEP1 as a prognostic biomarker and therapeutic target for oral cancer.
Authors: Takano Atsushi , Yoshitake Yoshihiro , Shinohara Masanori , Daigo Yataro
Published: May 2020

e18520

Background: Although current treatments for oral cancer (OC) include surgery, radiotherapy, and chemotherapy, their effectiveness is still limited. Therefore, the development of novel prognostic biomarkers and/or therapeutic agents is urgently needed. Methods: Our strategies are as follows: i) Identification of up-regulated genes in cancers by means of gene expression microarray, ii) Validation of clinicopathological significance of their protein expression by tissue microarray, iii) Examination of their growth effect on cancer cells by siRNAs and active ligand protein for growth assays. Results: We selected a secreted protein, OASEP1 (OC-associated serum protein 1) as a candidate. Real-Time qPCR and Western blotting showed that OASEP1 gene and its gene product were expressed in the majority of OC cells. Immunohistochemical staining showed that OASEP1 expression was observed in 73 (74.4%) of 98 OCs that had undergone curative surgery. In addition, high level of OASEP1 expression was associated with poor prognosis for OC patients ( P = 0.0158, by log-rank test). Suppression of OASEP1 expression by siRNAs for OASEP1 (si-OASEP1) significantly suppressed the growth and invasion of OC cell lines. Flowcytometry and live cell imaging showed that si-OASEP1 induced the apoptosis of OC cells. siRNAs against OASEP1-receptor also suppressed the growth of OC cells. Addition of active OASEP1 recombinant protein into culture media enhanced the growth of OC cells probably through AKT pathway. Our data suggest that OASEP1 and its receptor could play a significant role in the growth of OC cells in probable autocrine/paracrine manner. Conclusions: OASEP1 is a possible prognostic biomarker and therapeutic target for OC.
Performance of machine learning-augmented analysis of radiomics for the head and neck cancer histopathological diagnosis: A systematic review and meta-analysis.
Authors: Bisdas Sotirios , Seguin Jade , Roettger Diana , Yoneoka Daisuke , Shaikh Faiq
Published: May 2020

e18526

Background: The imaging criteria used for head and neck cancers (HNC) staging are mostly anatomical with basic quantitative measures, such as size, and admittedly radiologists’ reading of images is dependent on their expertise level. Radiomics, a term referring to extracting and investigating higher dimensional data from images, has been suggested to address these shortcomings. Assisted by machine learning (ML), highly efficient prediction models could revolutionise our diagnostic practices. Our goal was to study the role of ML in the histopathological diagnosis of HNC based on radiomics. Methods: A systematic review and meta-analysis was conducted using electronic databases (PubMed, Scopus, EMBASE, Google Scholar) and including MRI, PET, and CT studies in patients with HNC. Our study was aimed only at diagnosis utilising radiomics and artificial intelligence (ML). A PRISMA diagram retracing the steps of this search process was completed. QUADAS-2 and EQUATOR checklists were completed. A weighted mean, a mean and a median of the performance indicators were recorded. Results: 7 studies were found eligible for meta-analysis. Patient sample sizes ranged between 2-107 patients (median: 18). CT was the most common modality used (4/7 studies). All but one studies were retrospective. Support vector machine and random forest techniques were the main ML techniques used but how the model was built was rarely described. Furthermore, studies did not make clear the exact number of patients in the testing set. Other issues included the reporting of the final model performance with few studies reporting confidence intervals and 2 studies not reporting the exact performance metrics. The accuracy values for the testing set ranged from 58% -94.1%. The meta-analysis showed an overall weighted-mean accuracy of 78.53%, a mean of 82.9% and a median of 84.4%. The weighted mean of the sensitivity was 76.5%, the mean was 83.3%, and for specificity was 83.9% and 88.5%., respectively. The AUC was 0.8. The neuroradiologists’ overall accuracy was 50.4% if weighted, and 54.5% if not, and the corresponding accuracy of the ML classifiers were 78.4% and 79.6%. The ML scored an accuracy of 20% higher than the radiologists. Conclusions: The results are overall encouraging, keeping in perspective the possible calculation biases and small number of studies. There is need for better documentation and standardisation of the applied ML models, which show initially superior performance compared to radiologists.
Genomic landscape of head and neck cancers.
Authors: Subash Anand , Rao Vishal Uchila Shishir
Published: May 2020

e18530

Background: Head and neck squamous cell carcinoma (HNSCC) encompasses a heterogeneous group of tumours. In India it accounts for about 40% of all the malignancies. HNSCC in the subcontinent behaves differently as compared to the western world. As heterogenous as they are so are their response to treatment. Deciphering the human genome has indeed been one of the biggest contribution to science. Genomic profiling would help identify the variants that separate these HNSCC patients and facilitate development of newer targeted therapeutic strategies. Methods: At Healthcare Global Cancer Centre, Bangalore we retrospectively analysed 35 cases of Head and Neck squamous cell carcinoma as a pilot. Whole exome analysis of the patient samples were done using the Illumina Hi-Seq 2500 machine with a depth of 70-100X. Results: Of the 35 patients, 27 were oral cavity squamous cell carcinoma. About 2/3rd of these patients had history of tobacco or alcohol use. At the time of analysis 20 patients were alive and disease free,3 were alive with disease,11 were dead and 2 were lost to follow up. It was observed that the maximum number of variations were mis-sense mutations. Known oncogenic proteins like TP53 and NOTCH1 showed a mutation frequency of more than 50%, while DNA damage and repair genes like XRCC1 and ERCC2 were seen to have almost 90% mutation frequency, some of which have not been previously documented in literature. Conclusions: The preliminary data has brought to light some very novel mutations, many of them until now unknown to be implicated in HNSCC. This study holds the potential to predict response to treatment and factors which contribute to this. We have classified these novel mutations into different pathways so that specific targeted therapies can be developed in future.
Association of driver genes with high-tumor mutation burden and outcome in patients with head and neck cancer: Implications for immunotherapy.
Authors: Chen Yu , Chen Chuan-ben , Zheng Xiao-bin , Gao Xuan , Jun Liu , Xiong Jia-ni , Lin Jin , Xu Yaping , Guan Yan-Fang , Li Yi , Huang Yingying , Xia Xuefeng
Published: May 2020

e18533

Background: While the immune checkpoint blockades had demonstrated promising benefits in head and neck cancer (HNSC), its clinical efficacy is limited to a selected subset of less than 20% HNSC patients. Tumor mutation burden (TMB) has been reported as a predictor for ICBs in multiple tumors, including HNSC. However, the association of driver genes with TMB and outcomes in patients with HNSC has not yet been established. Methods: Somatic mutation landscape was characterized by interactively analyzed the sequencing data of 495 HNSC samples obtained from The Cancer Genome Atlas (TCGA) database and 185 samples from a Chinese cohort (Geneplus-database). Hybrid capture of a 1021 gene panel with potential clinical relevance was performed on tumor and paired Peripheral blood lymphocytes (PBLs) from 185 HNSC samples in a Chinese cohort. Results: In the Chinese cohort, patients harboring ≥5 muts/Mb (the top quartile of tTMB distribution) were classified as the TMB-H group; while ≥4.7 muts/Mb were classified as the TMB-M group. TMB -H was associated with better OS in the TCGA cohort. The rest were classified as TMB-L patients. Thirteen aberrant genes were significant correlation with TMB-H, including TSC2, POLE, CDK4, TSC1, MLH1, PTCH1, NF1, MSH3, RAD50, MSH2, CDH1, TNFRSF14, TERC. Among them,10 were further verified in the TCGA Head and Neck Cancer cohort, including TNFRSF14, MSH3, NF1, TSC2, RAD50, MSH2, PTCH1, POLE, MLH1, TSC1. Moreover, aberrant genes such as CDH1, MSH2 and RAD50 implicated better DFS (DFS:HR = .296, p = .034; HR = 0.128, p = .016; HR = .0422, p = .043) in HNSC of the TCGA cohort. Transcriptomic analysis in the TCGA Head and Neck Cancer cohort showed various degrees of immune upregulation in the tumor microenvironment (TME) in CDH1, MSH2, and RAD50 mutated population. Conclusions: These findings indicated that CDH1, MSH2, and RAD50 mutations may be associated with TMB-H, immuno-upregulation in TME and better survival outcomes. Combined with TMB, genes mentioned above may give us some insights into how ICB therapeutic strategies assist natural host immune responses against HNSC in Chinese population.
Effects of prexasertib, a CHK1 inhibitor, in the immune microenvironment of head and neck squamous cell carcinoma (HNSCC).
Authors: Chaudhary Ritu , Slebos Robbert , Song Feifei , McCleary-Sharpe Keegan , Masannat Jude , Tan Aik Choon , Wang Xuefeng , Amaladas Nelusha , Wu Wenjuan , Hall Gerald , Chung Christine H.
Published: May 2020

e18541

Background: Despite considerable advancements in the standard therapies including surgery, chemotherapy and radiotherapy, the clinical outcome for head and neck squamous cell carcinoma (HNSCC) remains poor due to tumor recurrence and metastasis. Molecular-targeted therapies have evolved as novel and promising treatment for HNSCC patients. Herein, we identified a CHK1 inhibitor, prexasertib, as a therapeutic target that enhanced the infiltration of innate and adaptive immune markers in the mice tumor immune microenvironment (TIME) and subsequently sensitizes the tumors. Methods: For this study we used syngeneic mouse model of HNSCC developed using mouse tonsil epithelial cells transformed with HRAS expression and PTPN13 knockdown to represent tobacco-induced HNSCC (MTE-Ras). In vitro drug activity of prexasertib was determined using immunoblotting, flow cytometry, cell proliferation and colony formation assays. The effect of prexasertib on TIME was quantified by Quantigene Plex panel and multiplex immunohistochemistry (mIHC). Results: We found that in vitro treatment with prexasertib increased the amount of DNA damage in the cancer cells and eventually lead to their death. Similarly, our in vivo data showed that treatment with prexasertib resulted in significant tumor regression and increased mice survival. At the molecular level, prexasertib treatment resulted in an upregulation of transcripts associated with T-cell activation, cytokines, chemokines and macrophages indicating an upregulation of inflammatory gene signature. This was further supported by our findings from mIHC staining of mice tumors showing increased infiltration of natural killer cells, natural killer T cells and dendritic cells, following prexasertib treatment. Interestingly, we also saw an increase in the Tregs after prexasertib treatment, which is indicative of an immunosuppressive environment, and we speculate this could be as a result of negative feedback following immune activation by prexasertib treatment. Conclusions: Our results uncover a previously unidentified role of prexasertib in regulating the innate and adaptive immune response in HNSCC, and therefore further corroborate CHK1 as a promising therapeutic target in HNSCC.
Survival for oropharyngeal and oral cavity cancer patients based on time to recurrence and HPV status.
Authors: Means Jeffrey , Stram Douglas , Katzel Jed Abraham
Published: May 2020

e18544

Background: It is unknown whether patients with recurrent oral cavity (OC) or oropharyngeal squamous cell carcinoma (OPSCC) have improved survival if the recurrence occurs beyond one year. We analyzed a cohort of recurrent OC/OPSCC patients to study survival outcomes stratified by time to recurrence and human papillomavirus (HPV) status. Methods: From a cohort of 3201 OC/OPSCC patients initially diagnosed between 1/1/2008 and 6/30/2019, 235 recurrent cases were identified. Time from the end of treatment until first recurrence was ascertained by chart review. HPV status was determined by HPV testing or based on anatomical site. Overall survival (OS) rates and median OS time after diagnosis of recurrence was evaluated across the time-to-recurrence and HPV groups using the Kaplan-Meier method. Differences in the survival curves tested for using the log-rank test. Results: 130 (56%) of the recurrent tumors recurred <1 year after end of treatment, and 104 (44%) ≥1 year. Patients with HPV-related tumors that recurred beyond one year had the best survival, with two-year OS at 0.62 (95% CI: 0.42-0.76), while patients with non-HPV related tumors that recurred <1 year had the worst survival, two-year OS of 0.38 (95% CI: 0.28-0.48). HPV-related tumors that recurred <1 year had roughly similar survival (two-year OS of 0.45, 95% CI: 0.30-0.59) to non-HPV-related tumors that recurred < 1 year (two-year OS of 0.51, 95% CI: 0.38-0.62). The log-rank test for difference in survival across time-to-recurrence and HPV groups was significant at p=0.03. Conclusions: In our cohort, patients with HPV-related head and neck cancer with recurrence ≥1 year had improved survival compared to all other recurrent head and neck cancer patients. In addition, our findings suggest that patients with HPV-related head and neck squamous cell carcinoma who recur prior to 12 months have long-term survival similar to patients with HPV-unrelated cancers. This has important implications for clinicians treating patients with recurrent head and neck cancer and may help guide the design of future clinical trials. [Table: see text]
Optimal cumulative cisplatin dose for radio-sensitization in locally advanced head and neck cancer.
Authors: Bhattacharjee Atanu , Noronha Vanita , Patil Vijay Maruti , Abhayankar Anuja , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar
Published: May 2020

e18553

Background: Evidence to choose the optimum chemotherapy between weekly and 3 weekly cisplatin for prolonging the duration of progression free survival in head and neck squamous cell carcinoma (HNSCC) is equivocal. This urged us to look into the cumulative dose of chemotherapy rather than the frequency of administration i.e. weekly or 3 weekly. The aim of this study was to determine the optimal cumulative dose of cisplatin to improve the progression-free survival (PFS). Methods: Between January 2011 and January 2018, a total of 836 consecutive patients with histologically proven primary squamous cell carcinoma of the oral cavity, larynx, hypopharynx, and oropharynx were included. The effect of the cumulative dose on progression-free survival was studied to obtain the optimal cumulative dose of cisplatin. Results: A total of 11 cohorts were generated to represent the cumulative doses. The cumulative doses were measured at 30, 60, 90,120,150,180,200,210,240 and 300 mg/m2 respectively. The maximum duration of progression-free survival (PFS) was considered to define the best effective cumulative dose. Conclusions: This study confirms that a cumulative cisplatin dose of ~ 210 mg/m2 is optimum for increasing PFS in patients with head and neck cancer. Therefore, doses with weekly 30 mg/m2 for seven cycles or 3-weekly 70 mg/m2 for 3 cycles could be equally effective to prolong the PFS. Clinical trial information: CTRI/2012/10/003062, CTRI/2014/09/004980.
Insulin-like growth factors in the blood of patients with oral squamous cell carcinoma receiving therapy with monoclonal antibodies (cetuximab).
Authors: Lyanova Aza A. , Frantsiyants Elena M. , Vladimirova Liubov Yu , Neskubina Irina V. , Surikova Ekaterina I. , Engibaryan Marina A. , Abramova Natalia A. , Popova Irina L. , Tikhanovskaya Natalia M. , Teplyakova Maria A. , Novoselova Kristina A. , Ryadinskaya Ludmila A. , Myagkova Valeriya S , Fomenko Yuriy A. , Kit Oleg I.
Published: May 2020

e18564

Background: IGF-1 and IGF-2 are powerful mitogenic factors with anti-apoptotic effect. Their overproduction leads to neoangiogenesis and metastasis. Monitoring the level of these factors can serve as a potential predictive tool. The purpose of the study was to study blood levels of IGF-1 and IGF-2 in patients with squamous cell carcinoma (SCC) of the oral cavity depending of the efficacy of chemotherapy (CT) and cetuximab. Methods: The study included 50 patients with squamous cell carcinoma of the oral cavity T3-4N0-1M0, stage III-IV. The main group (n = 30) received 2 CT cycles with cetuximab: cisplatin 100 mg/m2, intravenously, day 1, 5-fluorouracil 1000 mg/m2/day, intravenously, 96-hour continuous infusion, in combination with cetuximab 400 mg/m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15. The control group (n = 20) received 2 CT cycles: intravenous cisplatin 100 mg/m2 on day 1, intravenous 5-fluorouracil 1000 mg/m2/day, 96-hour continuous infusion on days 1-4. Results were compared with the values in 20 non-cancer donors. Levels of IGF-1 (mcg/L) and IGF-2 (ng/mL) were measured in the blood serum by ELISA using standard test systems (Mediagnost, Germany). Statistical analysis of results was performed using the Statistica 6.0 program (Stat-Soft, 2001). Results: Before treatment, levels of IGF-1 and IGF-2 in patients were lower than in donors by 53.5% and 20.3%, respectively. In patients with partial regression after CT, IGF-1 levels significantly increased by 33% (p < 0,05), compared to the values before treatment, while IGF-2 was both within donor and initial values and the IGF-1/IGF-2 ratio was similar to the initial level but 33.3% lower than in donors. The patients in the main group with partial regression normalized IGF-1 levels increasing it compared to initial values – by 87%. IGF-2 levels did not differ statistically significantly from the initial values and were 32.5% lower than in donors. The IGF-1/IGF-2 ratio was 58% higher than before treatment. Conclusions: CT and cetuximab normalized blood levels of IGF-1 in oral cancer patients with partial tumor regression.
Current trends in the management of lacrimal gland tumors: A National Cancer Database study.
Authors: Ashok Kumar Prashanth , Wang Dongliang , Sivapiragasam Abirami
Published: May 2020

e18573

Background: Lacrimal Gland (LG) tumors are rare with data limited to very few comparative trials. The original treatment is Orbital Exenteration followed by Radiotherapy (RT). Contemporary strategies like orbit sparing surgeries and Neoadjuvant Intra-arterial Chemotherapy (CT) are gaining popularity but remains controversial given the paucity of data. Our aim was to determine the pathological distribution and compare the treatment modalities used in LG tumors with the help of a large national database. Methods: From the 2004-2016 National Cancer Database (NCDB), we included Epithelial LG tumors. We excluded Lymphomas, Melanomas, Sarcomas and other metastatic lesions. Descriptive statistics, Hazard Ratio (HR) estimates and Kaplan Meier (KM) survival analysis were used. Results: A total of 669 LG tumors were identified. The distribution based on Pathology and treatment strategies used is represented in the table. The point survival estimate comparison between the surgical types and the various treatment groups showed no significance. Conclusions: SCC was the most common histological type. There was no difference in the overall outcome between radical and orbit sparing procedures. Adjuvant RT and adjuvant chemoradiation did not confer any additional survival benefit over surgery alone. Mallen-St Clair et. using the SEER database (321 LG patients) showed that RT improves Disease Specific Survival in SCC. Moving forward, larger population-based studies and prospective trials are needed to determine the most ideal management option. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator. [Table: see text]
Mental distress and mental health services receipt in foreign-born survivors of cancer: A national health interview survey analysis.
Authors: Arega Melaku A , Dee Edward Christopher , Muralidhar Vinayak , Nguyen Paul L. , Franco Idalid Ivy , Sanford Nina Niu , Mahal Brandon Arvin Virgil
Published: May 2020

e19001

Background: There is a greater burden of mental illness, in survivors of cancer compared with the general population. Though mental health interventions may reduce mental distress and improve subsequent oncological outcomes, there are disparities in mental health service (MHS) receipt in immigrant populations. Therefore, we examined contemporary patterns of mental distress and mental health service receipt by immigrant status in cancer survivors in the United States. Methods: Data are collected in non-institutionalized civilian adults by the US National Health Interview Survey. For this study, harmonized data of participants reporting a cancer diagnosis were extracted from the Integrated Health Interview Series from 2009-2018. Sample weight-adjusted estimates of mental distress were defined by the validated Kessler 6 (K6). MHS receipt in the past 12 months was estimated, stratified by K6 status. Multivariable logistic regression defined adjusted odds ratios (AOR) and 95% confidence intervals (95CI) for the odds of MHS receipt, with birth status (US vs. non-US) as the primary independent variable of interest. Results: Among 14,653 adult survivors of cancer and 207,018 adults without cancer, 4.16% vs. 3.01% had K6 >13, respectively (AOR 0.96, 95CI 0.87-1.07, P = 0.504). Among survivors of cancer, younger age, female sex, and white race were associated with K6>13, while factors associated with lower MHS receipt included non-US born status, non-white race, and older age. The distribution of severe mental illness (K6>13) did not differ by place of birth. However, non-US birth status was associated with lower MHS receipt among survivors of cancer with K6 < 13 (5.61% vs 8.15%, AOR 0.67, 95CI 0.49-0.92, P = 0.013), and there was a greater disparity among those with K6>13 (9.43% vs 37.8%, AOR 0.19, 95CI 0.08-0.45, P < 0.001) (Pinteraction= 0.002). Conclusions: In this large contemporary cross-sectional survey, though there was a similar distribution of mental distress in survivors of cancer based on birth status, non-US born adults with severe mental distress (K613) were 81% less likely to receive MHS relative to US born adults. These data suggest that immigrant survivors of cancer who suffer from severe mental distress may be a greater risk not receiving appropriate MHS, which could lead to subsequent adverse outcome. Given the demonstrated gap in use of MHS in non-US born adults with cancer and severe mental distress, increased efforts are needed to screen for mental illness and the need for MHS in immigrant populations.
Differences in real-world liver cancer treatment patterns among people living with HIV/AIDS (PLWHA) compared to those without HIV/AIDS (PWoHA).
Authors: Falkenstein Angelica , Klink Andrew J. , Gajra Ajeet
Published: May 2020

e19010

Background: Antiretroviral therapy (ART) has brought life expectancy among PLWHA on par with PWoHA, but the disparity in cancer incidence and mortality among PLWHA remains high. Hepatocellular carcinoma (HCC) is 4 times more common in PLWHA and an important cause of mortality. Guidelines now support treatment and management of cancer among PLWHA to follow those for PWoHA, but PLWHA have been excluded from registrational trials of novel agents. This study aimed to assess real-word differences in demographics and systemic therapy patterns for HCC among PLWHA and PWoHA. Methods: Adult patients with ≥2 claims for HCC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics, and comparisons across HIV status were made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 9,904 HCC PWoHA who received systemic therapy. Of 862 PLWHA with HCC, 162 (19%) received systemic therapy. PLWHA differed significantly from PwoHA: median age at diagnosis (60 v 63 years), male preponderance (84% v 71%), geography (Northeast, 41% v 19%; West, 22% v 45%), Charlson Comorbidity Score (median 7 v 1), depression (11% v 6%), chronic pulmonary disease (20% v 12%), liver disease (66% v 52%) and kidney disease (17% v 7%, all P< 0.05), respectively. First line (1L) therapy differed among PLWHA and PWoHA: sorafenib (34% v 25%), everolimus (1% v 4%), and doxorubicin-based regimens (42% v 33%; all P< 0.05). IOs were used in 1L and 2L among 584 (6%) and 223 (15%) of PWoHA and among 8 (5%) and 6 (19%) PLWHA, respectively (all P> 0.05). Median times from 1L start to 2L were numerically shorter among PLWHA and PWoHA (4.7 v 5.5 months; P= 0.77). The minority of patients among PLWHA and PWoHA continued onto 2L (20% and 15%, P> 0.05) and 3L (7% and 3%, P< 0.01), respectively. Conclusions: HCC is diagnosed at younger age among PLWHA v PWoHA. Important differences in comorbid disease burden in addition to HIV can impact clinical decision making in PLWHA. Future real-world research is needed to understand disparities in outcomes of PLWHA and develop guidelines specific to this group.
Material, psychological, and behavioral financial hardship and prostate cancer treatment type.
Authors: Tucker-Seeley Reginald , Tang Weizhou , Brown Colony , Bearse Jamie
Published: May 2020

e19013

Background: A prostate cancer diagnosis can have a significant financial impact on the family; and, the various treatment options present a variety of economic consequences. Treatments can present short- and long-term sequelae leading to additional therapies, and the costs for the household can vary depending on the type of treatment received. Cancer survivorship research has shown that many survivors experience financial hardship following diagnosis. Financial hardship has recently been conceptualized in cancer survivorship research across three domains: material, psychological, and behavioral. The material domain refers to the lack of financial resources (e.g. material hardship), the psychological domain refers to how one feels about the lack of financial resources (e.g. financial worry), and the behavioral domain captures the financial adjustments made in response to a lack of financial resources. The purpose of this study was to investigate the association between the material, psychological, and behavioral domains of financial hardship and the type of prostate cancer treatment received. Methods: The prostate cancer non-profit organization, ZERO - The End of Prostate Cancer, conducted an online “Prostate Cancer Education Survey” to determine information needs among individuals diagnosed with prostate cancer (N = 1,000). We used bivariate tests and simple and adjusted multivariable logistic regression models to test the association between financial hardship and the type of treatment received. Results: The results revealed no statistically significant differences across the treatment types for material hardship. Patients who received chemotherapy and primary hormone therapy had higher odds (OR = 1.84; CI: 1.01-3.33) of reporting psychological hardship compared to those reporting active surveillance/watchful waiting; and those reporting active surveillance/watchful waiting had higher odds (OR = 1.50; CI: 1.07-2.11) of reporting psychological hardship compared to those reporting surgery. Patients who received chemotherapy also had higher odds (OR = 2.52; CI: 1.30-4.88) of reporting behavioral hardship compared to those reporting active surveillance/watchful waiting treatment. Conclusions: Explicating the material, psychological, and behavioral correlates of prostate cancer treatment types provides greater specificity for potential intervention targets where programs can be designed for reducing specific types of financial hardship following prostate cancer diagnosis and during survivorship.
Racial and socioeconomic disparities in the treatment of resectable hepatocellular carcinoma.
Authors: Rho Young soo , Pagano Ian , Acoba Jared David
Published: May 2020

e19026

Background: Cancer surgeries performed at high case volume centers (hCVCs) are associated with improved surgical and clinical outcomes. Resectable hepatocellular carcinoma (rHCC) is not common in the US and the impact of surgery at hCVCs has not been well assessed. We analyzed the impact of surgery at hCVCs on survival, and the potential racial and socioeconomic disparities associated with obtaining care at hCVCs. Methods: We collected demographic, diagnostic, treatment, and survival data of 96,215 patients with stage I-III HCC diagnosed between 2004 – 2015 from the National Cancer Database. To estimate the average surgical volume/year, number of reported cases were divided by the number of years the facility was represented in the database. Logistic regression was used to determine the associations between case volume, facility type and the demographic and clinical variables. We assessed demographic and clinical predictors of overall survival (OS) using Cox proportional hazards regression. Results: In total, 10,419 resected HCC patients were included in the analysis. The median age was 64 (18 – 90), 68.4% were male and 69.5% were white. Facilities were divided into quartiles by average number of surgical CV/year: 1st quartile (1Q) 0.08-1.60, 2Q 1.61 – 3.91, 3Q 3.92 – 8.34, and 4Q 8.35 – 45.34. In a multivariate model, improved OS was seen with each increase in quartiles with the highest CVCs (i.e 4Q) HR 0.70 (95% CI 0.63 – 0.77). Treatment at academic centers did not show an OS advantage (HR 0.93; 95% CI 0.86 – 1.01). Factors including black race (OR 0.83; 95% CI 0.75-0.93), age 65+ (OR 0.91; 95% CI 0.82 – 1.00), and living in a metro area with a population of 250,000 – 1 million people (OR 0.68; 95% CI 0.62 – 0.74) were less likely to be associated with treatment at hCVCs. Conversely, Asians/Pacific Islanders (OR 2.28; 95% CI 2.04 – 2.55) and those with private insurance (OR 1.33; 95% CI 1.18– 1.40) or Medicare (OR 1.21; 95% CI 1.05 – 1.38) were more likely to be treated at hCVCs. Conclusions: rHCC is not common in the US and having surgery at hCVCs improves OS. However, racial and socioeconomic disparities exist in receiving care at these hCVCs.
Incidence of colon cancer in younger population and lower incidence in Asians and females in central balley of California: Health disparity and epigenetic study model.
Authors: Sodavarapu Soujanya , McGrew Tyler , Hobbins Mark , Haddad Sami , Ramdass Prakash , Obad Nashwan , Gill Amandeep Singh , Vyas Dinesh
Published: May 2020

e19028

Background: California acts as a boiling pot for immigration and the perfect ecosystem to study epigenetic changes from dietary and environmental factors in various ethnicities. It has a significant immigrant population, with approximately a quarter of the 40 million residents being foreign-born. The impact of migration on colon cancer incidences over time has not yet been characterized on a broad-scale level in the Northern Central Valley. This provides a unique opportunity to study the influence of migration, socio-economic gradient, environmental, and racial identity on the incidence of cancer in a subset of California’s San Joaquin County Population. Colon cancer affects around 100,000 annually, with white and African Americans being more often affected than Asians or Hispanics. Methods: This study is a retrospective, single-institution study that compared the socio-demographic variables and clinical characteristics of the patients who had a history of colon cancer in an academic central valley institution. We reviewed all the patient charts with a diagnosis of colon cancer from 2014-2019 and compared the age, demographics, socioeconomic status, comorbidities, pathology, treatment, and outcomes in the population. Appropriate statistics have been used for analyzing the data. Results: A retrospective chart review of all patients diagnosed with colon cancer from our Hospital from 2014-2019 which revealed that 23.9% of patients were younger than 50 years at diagnosis, and mean age of diagnosis is 56.6 years, compared to the national average where younger population constituted at 11% and mean age for men and women are 68 years and 72 years respectively. 36.5% were 50-60 years old, and 39.2% were > 60 years old. Women constituted 31% in our group compared to compared to 35.6% nationally. Asians are 23% of the central California population, but only 11.4% of patients in our group of colon cancer patients were Asian/pacific islanders, with 6.4% being average weight. 36.7% of patients have obesity. 67.4% were > 25 BMI, of which 12.8% were younger Hispanics with BMI 25-30. Adenocarcinoma is seen in 91.4% of patients. Conclusions: The younger population with male predominance is seen. Asians see a surge in colon cancer incidence, but the incidence rate is still lower. Epigenetic, western lifestyle, and environmental are responsible factors. Younger overweight Hispanics are increasing in number as well. We will present further subgroup analysis at presentation.
Impact of US population demographic changes on projected incident cancer cases from 2019 to 2045 in three major cancer types.
Authors: Nguyen Jimmy , Napalkov Pavel , Richie Nicole , Arndorfer Stella , Zivkovic Marko , Surinach Andy
Published: May 2020

e19044

Background: The United States (US) Census Bureau has forecasted an unprecedented shift in the US demographics by 2045, in which there will be no single majority race/ethnicity. Due to well-characterized health disparities among different races/ethnicities in oncology and projected demographic changes, it is of interest to assess changes in the burden of three most frequent cancers: breast cancer (BC) for women, prostate cancer (PC) for men, and colorectal cancer (CRC) for both genders between 2019 and 2045. Methods: Historical age-adjusted rates (AARs) for BC in women, PC in men, and CRC in patients of all ages and stratified by race/ethnicity were collected from the SEER 18 database for 2000-15 period. AARs for cancers of interest were analyzed in Joinpoint Regression Program to obtain an average annual percent change (AAPC) for 2000-15. AARs were then projected to 2045 by assuming the rate behavior is equal to the AAPC. Projected absolute cases per 100,000 were generated by multiplying projected AARs with the associated projected population, retrieved from the US Census Bureau 2017 National Population Projects, and dividing by 100,000. The absolute change in projected patient numbers of cancer cases by race/ethnicity were assessed between 2019 and 2045. Results: From 2019 to 2045, a decrease of 4% is expected in the White Non-Hispanic (WNH) population while the Black (B), Hispanic (H), and Asian/Pacific Islander (API) populations are projected to increase 24%, 54%, and 57%, respectively. In the same time period, the projected number of BC incident cases for women of all ages decreased by 1% in WNH while the B, WH, and API populations were projected to increase 72%, 98%, and 120%, respectively. In both genders of all ages, a 39% and 17% reduction in the number of CRC incident cases in the WNH and B is expected compared to a 61% and 11% increase in the WH and API populations, respectively. Given observed reduction in PC incidence, especially in men 65+, the number of incident PC cases is projected to decrease by 2045 for all included races/ethnicities. Conclusions: Among racial and ethnic minorities, an increase in the number of BC and CRC cases is expected between 2019 and 2045. Projected decrease in PC cases is likely a result of decrease in incidence rates between 2010 and 2015 and should be assessed as new data become available. Currently, racial and ethnic minorities comprise < 20% of patients enrolled in clinical trials, demonstrating the need to understand biologic and social underpinnings of disparities in clinical outcomes in underrepresented groups.
Explorative analysis of expanded access for intermediate-size and larger patient populations.
Authors: Krendyukov Andriy
Published: May 2020

e19070

Background: Cancer is a major public health problem worldwide and is the second leading cause of death in the USA. While continuous efforts are being made by the US Food and Drug Administration to bring more new oncology products (NOP) to patients, there is a high unmet medical need for oncology patients to get access to care, and in particular access to NOP outside of clinical trials before the NOP is approved or commercialized. To improve access to NOP, several pathways are endorsed by competent authorities including: early dialogue with regulatory agencies; accelerated assessments; conditional marketing authorization; and early access provision, known as expanded access (EA) in the USA and compassionate use (CU) in the EU. Methods: A literature search and explorative analysis of available EA data from Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) relating to submission and approval of existing or investigational new drugs (IND) was performed for individual (single) patient emergency and non-emergency IND (IPIND), intermediate size IND (ISIND), and treatment IND (TIND). The findings were compared to centralized CU programs. The analysis was primarily focused on understanding the current landscape of EA for patient groups compared with individual patient categories. Results: Based on available CDER and CBER data submissions for ISIND and TIND categories were dramatically low compared with IPIND and total applications for EA: 1.25% (ISIND) and 0.13% (TIND) out of 1,598 EA applications received in 2018; and respectively 2.7% and 0.11% out of 1,741 EA applications in 2017; 2.6% and 0.24% out of 1,634 EA applications in 2016; 3.6% and 0.15% out of 1,328 EA applications in 2015; and 2.8% and 0.05% out of 1,886 EA applications in 2014. A high approval rate was reported for all three EA categories, and in particular approval of 95% (174 out 183) for ISIND and 100% (1 application) for TIND by CDER, and approval of 89% (24 out of 27) for ISIND and 80% (8 out of 10) for TIND by CBER. No applications for CU were reported by the European Medicines Agency for the same period of time, however several oncological products have been approved for CU in some European countries. Conclusions: Despite high approval rates, applications for ISIND and TIND remain low, especially in comparison to IPIND. In the absence of, or limited, alternative treatments, access provision to patient groups such as ISIND and TIND in the USA, and CU in the European Union, might represent an underutilized opportunity for oncological patients to obtain early access to care.
Comparison of advanced care discussions between Chinese-American and Caucasian stage IV cancer patients at a single American cancer center.
Authors: Glover Avery , Schroeder Courtney , Ernst Emma , Vesel Tamara
Published: May 2020

e19081

Background: Timely discussions with cancer patients on prognosis, goals of care (GOC), and end-of-life care (EOLC) are essential components of quality care for diverse populations. Although Chinese-Americans represent one of the fastest growing ethnic groups in the United States, little is known about the utilization of these advanced care discussions with Chinese-American cancer patients. Methods: In this exploratory review, we collected data for 63 Chinese-American and 63 Caucasian stage IV solid cancer patients at a tertiary medical center who died 2013-2018. The following data points were compared: frequency and timing of prognosis, GOC, and EOLC discussions; family inclusion in discussions; healthcare proxy identification; DNR completion. Results: Chinese-American and Caucasian patients had similar frequencies of prognostic (76% vs 71%), GOC (51% vs 56%), and EOLC discussions (89% vs 84%). For all three types of conversations, Chinese-American patients had the discussions earlier on average (days before death: prognosis 86 vs 62; GOC 54 vs 37; EOLC 69 vs 48) and included family members in the discussions more often (30% vs 15%). Chinese-Americans identified healthcare proxies earlier (50 vs 45 days before death). Chinese-Americans had DNR orders placed later (29 vs 33 days before death) and were more likely to have DNR orders placed on the day of death (30% vs 23%). Conclusions: Despite similar frequency of advanced care discussions, earlier conversations, and earlier identification of healthcare proxies in the Chinese-American group, DNR orders were placed later and were often delayed until the day of death for Chinese-American patients. Further studies are needed to better explore the differences indicated in this preliminary study.
Effect of race and insurance status on stage at diagnosis and overall survival of triple-negative breast cancer (TNBC): Analysis of the National Cancer Data Base (NCDB).
Authors: Khan Rafiullah , Abuali Inas , Vick Eric J. , Smart Luke , Xie Changchun , Charif Mahmoud
Published: May 2020

e19086

Background: TNBC is a heterogeneous sub-type of breast cancer characterized by younger age of onset, more aggressive course, and higher incidence among African Americans who also experience disparities in access to health care including health insurance coverage and cancer screening. Methods: We performed a retrospective analysis of the NCDB to study the impact of race and insurance status on the stage at diagnosis and overall survival of people with TNBC. Chi-square tests analysis was used for univariate analysis. Cox models were used to test for survival differences between race and insurance status adjusted for other covariates such as age at diagnosis, gender. Results: Among 1,148,016 people with TNBC registered in the NCDB from 2010 to 2016, 87.7% were identified as white and 12.3% were identified as black. The majority (99%) were female. Mean age at diagnosis was 62.0 years for females and 65.9 years for males. Among white patients, 1.8% were uninsured while 3.6% of black patients were uninsured. Advanced stage at diagnosis was less common among white people (9.4%, Stage 3; 4.9%, Stage 4) than black people (13.3%, Stage 3; 7.6%, Stage 4). Uninsured patients had more advanced disease at time of diagnosis (16.2%, Stage 3; 14.1%, Stage 4) than insured patients (9.8%, Stage 3; 5.0%, Stage 4). Overall survival after adjustment for age at diagnosis, gender and insurance status was greater for white patients compared to black patients (harm ratio 0.60). Overall survival after adjustment for age at diagnosis, gender and race was lower for uninsured patients than insured patients (harm ratio 2.25). Conclusions: Racial disparities significantly affect TNBC patients, with black women having lower insurance coverage and worse overall survival. [Table: see text]
Factors affecting time to treatment in hepatocellular cancer.
Authors: Seegobin Karan , Majeed Umair , Ritter Ashton , Wylie Natasha , Starr Jason Scott , Jones Jeremy Clifton , Mody Kabir
Published: May 2020

e19088

Background: Significant disparities in the stage at diagnosis and survival outcomes exist between various groups diagnosed with hepatocellular carcinoma (HCC) based on sex, race, insurance coverage, and marital status. Previously published data shows disparities more in patients who are African-American, Asian and low income. Little data has been published on factors that influence timeliness to treatment initiation in patients diagnosed with HCC. Methods: Retrospective analysis was performed on 96,586 patients diagnosed with HCC from 2004-2014 using data in the National Cancer Database (NCDB). Time to treatment was divided into two categories: ≤40 days (early, n = 66322) and > 40 days (late, n = 30264). We carried out univariate and multivariate analyses to compare demographic, clinical, treatment, and facility-related factors influencing the timeliness of treatment initiation in HCC. Results: Univariate analysis revealed a significant difference in time to treatment initiation based on age, race, income, insurance status, type of area, geographic region, type of facility, and cancer stage (P < 0.001). Multivariate analysis showed that household income < $30,000/year, Pacific region, urban area of residence, black race, age 70-79 years old or ≥80 years old, academic centers, stage II disease and medicaid insurance were all factors with longer time to treatment initiation. Discussion: HCC is the sixth most common cancer and the second leading cause of cancer mortality worldwide. The 5-year relative survival for localized, regional, and distant stages are 32.6%, 10.8% and 2.4% respectively. In our results we noted significant disparities in time to treatment with respect to various socioeconomic factors. These results are comparable to that reported in other cancer types. Further subgroup analysis of our data shows 2581 patients who received their first treatment after 200 days. In a similar study done in Taiwan, those treated more than 181 days and 61–180 days after diagnosis had a 1.68 and a 1.39 increased risk of death respectively, which were statistically significant. Many factors contribute to delayed treatment, some of which are difficult to circumvent, however where possible efforts should be made to overcome these. Conclusions: Various socioeconomic factors were found to affect the time to treatment initiation in HCC patients. The next step would be to strategically implement policies and practices to address these factors.