bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of various subtypes of circulating DNA in ovarian cancer patients.
Authors: Minarik Tomas , Vlkova Barbora , Kalavska Katarina , Manasova Denisa , Kubickova Michaela , Jurik Andrej , Lengyel Tibor , Slezak Igor , Sadovsky Oliver , Niznansky Bohumil , Krkoska Milan , Kocova Lucia , Mardiak Jozef , Sufliarsky Jozef , Celec Peter , Mego Michal 
Published: September 2018

e17092 Background: Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Circulating tumor DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of circulating DNA in advanced ovarian cancer. Methods: This prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and bevacizumab (42 pts). Thirty-five patients had optimal debulking before chemotherapy. Circulating plasma DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts). Results: Total extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR=0.35 (0.14-0.86)) and overall survival (HR=0.18 (0.04-0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis. Conclusions: Our data suggest that ecDNA of both, nuclear and mitochondrial origin, could be added to prognostic markers in ovarian cancer. This is of importance as this analysis does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Analysis of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.
Survival disparity and racial differences in the use of neoadjuvant chemotherapy (NAC) compared with primary debulking surgery (PDS) in women with ovarian cancer.
Authors: Miller Eirwen M , Tymon-Rosario Joan , Xie Xianhong , Smith Harriet Olivia , Goldberg Gary L. , Kuo Dennis Yi-Shin , Nevadunsky Nicole Suzanne 
Published: September 2018

e17099 Background: Studies demonstrate racial disparity in ovarian cancer survival though survival differences seem to be mitigated when patients receive similar care. We sought to identify whether racial disparity exists in the use of NAC or PDS for women with ovarian cancer. Methods: After IRB approval, all patients with epithelial ovarian cancer who received primary treatment at our institution from 2005-2016 were identified from our tumor registry. Charts were retrospectively reviewed for clinicopathologic and survival data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Kaplan-Meier was used to compare survival probabilities. Results: 302 evaluable patients were identified. 240 (79%) patients underwent PDS and 62 (21%) received NAC. Older patients, black patients, and those with stage III/IV disease were more likely to receive NAC. In a multivariate analysis controlling for stage and age, black race remained associated with NAC [OR 3.25 (95% CI 1.41-7.47), p < 0.01]. In a subgroup of advanced disease, stage III patients (n = 138) were more likely than stage IV patients (n = 52) to undergo PDS (78% v 44%, p < 0.01) and black patients were more likely than others to present with stage IV disease (39% v 22%, p = 0.01). NAC was utilized more frequently (48% v 24%, p < 0.01) in black patients compared with all other races. In the advanced stage subgroup analysis, patients that underwent PDS had a longer PFS than those that received NAC [HR 2.21 (95% CI 1.26-3.89), p = 0.01]. Conclusions: Racial disparity exists in the selection of PDS compared with NAC for patients with ovarian cancer and this disparity persists when controlling for stage and age. The choice of NAC or PDS may result in survival disparity. Further investigation is needed to examine other reasons, such as medical co-morbidities and disease distribution, for racial disparity in management. [Table: see text]
Acceptability of FitBit activity trackers for socioculturally diverse endometrial cancer survivors: A pilot study.
Authors: Miller Eirwen Murray , Rossi Amerigo , Samuel David , Ramirez Carolina , Viswanathan Shankar , Kuo Dennis Yi-Shin , Nevadunsky Nicole Suzanne 
Published: September 2018

e17103 Background: Endometrial cancer survivors are the least physically active of all cancer groups. In past feasibility studies of a physical activity intervention for obese endometrial cancer survivors, we have found high adherence and significant improvements in quality of life and body composition but low recruitment (48%). The primary objective of this study was to assess the acceptability the FitBit Alta activity tracker among socioculturally diverse endometrial cancer survivors. Methods: After IRB approval, patients were approached for study participation at the time of routine follow-up in gynecologic oncology clinic. Eligible patients included those with a history of stage I-IV endometrial cancer diagnosed within the past 10 years who were not undergoing active therapy at the time of study participation. Participants were instructed to wear a FitBit Alta for 30 days. At the conclusion of the study period, patients received a phone call to complete an acceptability questionnaire. After 30 days of use, the FitBits were returned to provide detailed daily activity data for the duration of the study period. Results: Of 37 eligible identified patients, 30 agreed to participate in the study (81%). Recruitment to this study was significantly higher as compared with our historical exercise lifestyle intervention (48%, p < 0.01). Mean age was 65 and BMI 33 kg/m2 (19-64kg/m2). 70% reported stage I and II disease. Patients self-identified as 53% white, 23% black, and 33% Hispanic. 40% of patients had household incomes < $60,000 per year. Preliminary data shows that patients walk between 2,500 and 12,000 steps per day. Conclusions: Recruitment to the FitBit Alta was significantly higher than historically reported exercise lifestyle interventions at our institution. Additional research is needed to understand retention and patient satisfaction with lifestyle interventions using wearable technology.
Incidence and epigenetic factors associated with endometrial cancer in Appalachian Kentucky.
Authors: Manda Rohini , Raja Naga Praneeth , Shankar Uday , Dignan Mark , Kandagari Nagapavani 
Published: September 2018

e17113 Background: Data from the US Cancer Statistics Working Group shows that the age-adjusted incidence of endometrial cancer was 25.6/100,000, 2009-2013 for the US and 24.9/100,000 for the Commonwealth of Kentucky. However, for the Kentucky River Area Development District (KR) in the Appalachian region, the rate was higher at 34.2/100,000. This investigation was designed to explore epigenetic factors related to the elevated incidence of endometrial cancer in the KR region of Kentucky. Methods: With IRB approval, retrospective data on women with endometrial cancer were abstracted from tumor registry records for the period 2005-2015. Data including age at diagnosis, family history of cancer, smoking, diabetes and demographic characteristics were analyzed using SPSS. Results: Data on 41 cases of endometrial cancer from 2005-2015 were included in the analyses. The age range was 37-87 with mean age 62. Of the 41 cases, 19.5% (8/41) were under age 50 at diagnosis. 2 out of 8 (25%) had family history of Lynch syndrome associated malignancies. 9 (22.0%) had family history of cancer. No significant associations between smoking, age at diagnosis and diabetes were noted. Conclusions: There is an increased incidence of endometrial carcinoma in Appalachian Kentucky in general, and elevated rates in women under age 50 compared to statewide and US rates. We have shown from our previous research that there is a higher incidence of lynch syndrome among young patients with colon cancer in Appalachian Kentucky. Similar findings were observed with endometrial cancer from this analysis. Further evaluation and genetic testing for any association with Lynch syndrome in this age group is needed.
Prognostic significance of performance status in patients with head and neck squamous cell carcinomas (HNSCC) receiving immune checkpoint monoclonal antibodies (ICmAB) in a single institution.
Authors: Hwang Victoria , Martins Renato G. , Eaton Keith D. , Chow Laura Quan Man , Baik Christina S. , Goulart Bernardo H. L. , Lee Sylvia Mina , Santana-Davila Rafael , Rodriguez Cristina P. 
Published: September 2018

e17506 Background: The anti-PD1/-PDL1 ICmABs can result in objective responses in some (13-20%) patients (pts) with HNSCC. We evaluated clinical factors that may predict oncologic outcomes. Methods: We identified pts who received an ICmAB at our institution and retrospectively collected demographic, tumor, treatment, progression, and survival data. The Kaplan Meier method was used to estimate survival. Log-rank and Wilcoxon tests were used to explore associations between clinical features and outcomes. Results: 55 pts received ICmAB in a clinical trial at our center from 8/2012 to 12/2016. The median age was 64 years, 13 (24%) were female, and 45 (82%) were white. ECOG Performance Status (PS) was 0 and 1 in 23 (42%) and 32 (58%) pts, respectively. 29 (53%) were current/former smokers who smoked a median of 20 (range 0-70) pack years. Primary sites included: oropharynx (OP) 31 (56%), oral cavity 9 (16%), nasopharynx 6 (11%), nasal cavity 3 (5%), hypopharynx (HP) 2 (4%), unknown (UK) 2 (4%), and skin 2 (4%). 28 (51%) were p16+, with the following primary sites: OP in 26, UK in 1, and HP in 1. 53 (96%) received prior curative intent therapy. A median of 2 (range 0-5) lines of systemic therapy (including curative intent) were given prior to ICmAB initiation, and 31 received an ICmAB as a single agent. There were 19 (35%) objective responses with 1 complete response, and 14 (25%) had stable disease. With a median follow-up of 12 months (m), the median overall survival (OS) was 15m (95% CI 11,47), and median time to progression was 4m (95% CI 2.2, 6.8). An ECOG PS of 0 vs 1 was associated with superior OS (36m vs 11m p = 0.001). Tobacco use, p16+ disease, single agent ICmAB vs. combination, number of lines of prior systemic therapy, or radiation therapy within 3m prior to ICmAB initiation did not appear to have a relationship with survival. Conclusions: A PS of 0 predicted for more favorable OS among HNSCC pts receiving ICmAB in this single center retrospective cohort. In contrast to data with chemotherapy, established prognostic markers (including p16+ and limited/no tobacco use) did not appear to impact survival.
Next generation sequencing of cell free circulating tumor DNA in blood samples of recurrent and metastatic head and neck cancer patients.
Authors: Porter Ashleigh , Daniels Gregory A. , Patel Sandip Pravin , Sacco Assuntina Gesualda , Banks Kimberly , Cohen Ezra E.W. 
Published: September 2018

e17516 Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is an increasingly prevalent disease but effective targeted therapy is lacking. The use of next generation sequencing (NGS) in the identification of novel targets has been suggested as a way to potentially expand therapeutic options and thereby improve outcomes. Methods: Data was collected on patients with recurrent and metastatic (R/M) head and neck cancers who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene circulating tumor DNA (ctDNA) NGS platform. CtDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures. Results: 60 HNSCC patients were evaluated from February 2015 to June 2016. The most common tumor type and histology was oropharyngeal squamous cell carcinoma (n = 21), which was commonly human papillomavirus (HPV) positive (n = 15). Other cancer types included salivary gland and thyroid cancers. The most common mutations identified by ctDNA analysis were TP53 (98%), PIK3CA (43%), NOTCH1 (38%), and ARID1A (36%). These findings were consistent with results from tumor sequencing data (n = 29) where TP53 (48%) and PIK3CA(24%) were also reported with the highest frequency. Importantly, 73% (n = 22) of patients had alterations identified in ctDNA that were not present in tumor specimens. Actionable mutations were identified in 66% of HNSCC and in 50% salivary gland cancer patients. Of patients with actionable mutations, 10% (n = 6) received matched targeted therapy (MTT): 3 (50%) had stable disease (SD), 1 had progressive disease (PD), and 2 were not evaluated. Of those who did not receive targeted therapy (n = 23), 1 (4.3%) patient had a complete response treated with immunotherapy, 11 (47%) had SD, and 11 (47%) had PD. Conclusions: Analysis of ctDNA may play a role in management decisions in R/M HNSCC. The majority of patients had unique mutations identified on ctDNA. The utility of ctDNA NGS and its role in patient management should be explored in future studies.
Clinical evaluation of circulating tumor cells in locally advanced nasopharyngeal carcinoma: A prospective study.
Authors: Wu Yuan , Qian Yu , Peng Jun , Wei Xueyan , Yuan Zilong , Zhou Fuxiang , Hu Desheng 
Published: September 2018

e17523 Background: Circulating tumor cells (CTCs) have been showed to correlate with curative effects and prognosis in many cancers, but there are few data describing the importance of CTCs in nasopharyngeal carcinoma (NPC). Our aim was to prospect the karyotyping of CTCs and the correlation between CTCs and clinical response in patients with locally advanced NPC. Methods: Serum was collected in 82 patients with locally advanced NPC. CTC was measured by negative enrichment with immunostaining of CD45, DAPI and imFISH with the centromere of chromosome 8 probe (CEP8) method. Cells with CD45-/DAPI+/CEP8 ≥3 were defined as positive CTCs and the karyotyping of chromosome 8 in CTCs were identified as triploidy, tetraploidy and multiploidy. Patients were treated with 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy according to the clinical trial (NCT 02562599). CTC was also measured after each cycle of chemotherapy. Clinial response was classified according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) criteria. Results: Positive CTCs were detected in 42 of 82 patients prior to treatment. They were independent with age, sex, smoking and clinical stages. Continuous CTC detection of 30 enrolled patients with positive CTCs showed that the ratio of CTCs and CTCs with different ploidies significantly decreased after therapy (P < 0.05). Although the change was not correlated with clinical response (P = 0.054), the decreases in CTCs count of patients who had complete response (CR) to the treatment were significant (P < 0.05), while the decreases of CTCs count of patients who had partial response (PR) were not (P > 0.05). Further analysis indicated that CR patients had fewer tetraploidy CTCs prior to the therapy than PR patients (P < 0.05). Moreover, tetraploidy CTCs count also indicated a positive prediction value for clinical response to treatment according to maximum likelihood estimation (P = 0.045, 95%CI [1.032,18.060]). Conclusions: The decrease of CTCs is correlated with a better therapeutic efficacy in patients with locally advanced NPC and the number of tetraploidy CTCs before treatment could be used as a predictive factor for clinical outcomes.
The demography of human papillomavirus (HPV) infections in oropharyngeal cancer patients from 2011-2016: A single Veteran Administration institution.
Authors: Dawson George Anthony , Zhang Yue Hua , Laurio Angela , Smith Patricia , Dellatto Michael , Innis-Gordon Fiona T. , Reino Anthony 
Published: September 2018

e17532 Background: Human papilloma virus (HPV) is a known biologic (viral) carcinogen and has a predilection for tissue in head and neck sites- HPV types 16/18. Current NCCN guidelines recommend HPV testing on newly diagnosed cancers - Head and Neck region - specifically the oropharynx. Methods: After IRB approval, data from our center ranging from 01/01/2011 to 12/31/2016 were collected by using international classification codes (ICD-9) 142, 143, and 146. We enrolled 81 patients for review from of these anatomic sites: Base of tongue, Tonsils, Posterior hypo-pharyngeal wall, soft palate and unknown primary + neck nodes. Data collected: HPV status / age / stage at diagnosis. Risk factors collected were marital status, ethnicity, age, alcohol and tobacco use, and other co-factors. Results: A total of 73 of 81 cases met our criteria for inclusion into review: excluded - 5 with Non-Hodgkin’s lymphoma; 1 with plasma cell neoplasm; 2 excluded - p16 testing only. All enrollees were male. Age range 45 - 91. Mean age: HPV + 64.11 / HPV – 66.76yrs. Anatomic site:BOT-35(48%) /Tonsil-25 (34%) /unknown primacy- 6(8%) /Soft palate– 4(0.05%) /Hypo-pharnyx-3(0.04%). Ethnicity: Non-Hispanic White– 32(44%) /Black-19(26%) /Hispanic – 20 (27%) /American Indian – 1(0.01%) /Unknown – 0. Seventy-three tested for HPV: 36 pos (49%) /37 neg (51% ). Whites were of 49% HPV+. HPV16/18+ in 34 of 36 (94%) tumors. Tobacco exposure ever:32/37(75%) HPV + and 26/36 (75%) HPV - groups. Alcohol use ever: HPV+ 75%; HPV – 67%. Location:BOT/Tonsils were 32/36 (80%) HPV+ cases and 27/37(73%) of HPV – cases. HPV + Marital status: Married 9 (26%) / Never mar 9/Divced 15/Sep 2/Wid 1 - 74% not married. HPV – 37: Married 12 (32%) /Never mar 9 /Divced 9/Sep 5/Wid 2 – 68% not married. Conclusions: HPV +16/18 (34 of 36) infections in our patients (73) were 49% of the overall group. BOT and Tonsil cancers most were the common sites in both groups (+/-). Compared to non-VA patients, our HPV + group used more alcohol and smoked more, and were older - though both groups (+/-) had high usage rates. We noted more divorcees, and lower marriage rate in the HPV+ group. Whites were 44% overall but 49% of HPV + group.
Computer extracted features of nuclear architecture in H&E sections to predict disease recurrence in oropharyngeal squamous cell carcinoma patients.
Authors: Lu Cheng , Lewis James , Madabhushi Anant 
Published: September 2018

e17536 Background: Most patients with oropharyngeal squamous cell carcinoma (OPSCC) are cured of their disease but 10-20% will develop recurrence. Identifying high risk patients is key to tailoring therapy and reducing treatment-related morbidity. In this study, we present initial findings using computerized analysis of local nuclear architecture from digitized H&E tissue sections of OPSCC via a new algorithm called cell run-length features (CRF) to distinguish patients with more versus less aggressive disease. Methods: H&E stained tissue microarray sections of 160 primary p16+ OPSCC were digitally scanned. Our CRF analysis involved 1) nuclei segmentation, 2) creation of local cell cluster graphs based on proximity of nuclei, and 3) computing CRF for each cell cluster graph. The CRF reflects the total number of different ways/runs that the graph vertices can be traversed. A higher CRF reflects more complex nuclear spatial architecture, while a lower CRF reflects the converse. A series of CRF features relating to statistics of the graph runs across the image are then extracted,. The top 5 predictive features were identified via Wilcoxon Rank Sum Test and then evaluated in conjunction with a binary quadratic classifier via 5-fold cross validation. Results: The top ranked features were related to CRF non-uniformity (i.e. reflecting the variation of complexity of different nuclei clusters) and the classifier yielded a mean area under the receiver operating characteristic curve of 0.75 in discriminating patients who did and did not have disease progression. Patients with high risk CRF values were 5.7 times more likely to suffer disease recurrence than those without. While the whole cohort had a disease recurrence rate of 12.5%, those with low CRF values developed recurrence in only 1.875%. Conclusions: CRF features demonstrate a strong association with disease recurrence in patients with p16 positive OPSCC. Our preliminary findings suggest that measurements related to local arrangement of nuclei have potential in the risk assessment of patients with p16 positive OPSCC. The findings will need to be independently validated in a separate, powered cohort of patients.
Towards mapping immune responses of nasopharyngeal carcinoma in Saudi Arabian patients, single institution experience.
Authors: Al-Rajhi Naser , Soudy Hussein , Mohammed Shamayel , Khoja Hatem , Ghebeh Hazem 
Published: September 2018

e17541 Background: The prevalence of Nasopharyngeal Carcinoma (NPC) is higher in Saudi Arabia compared to western countries. Genetic susceptibility and/or environmental factors (like infection with Epstein-Barr virus) contribute to the development of this tumor. There is a lack of information on the expression of markers related to the immune response in Saudi NPC patients. Methods: Here we report on profiling of two cohorts of NPC cases from patients treated at King Faisal specialist hospital & Research cneter (KFSH&RC) using the most relevant immune markers. The first cohort included 54 patients with local NPC while the other cohort included 25 cases of metastatic NPC at presentation. Immunostaining was done using Ventana benchmark fully automated system. Two anatomical pathologists (SM & HK) scored the NPC cases for CD3+ infiltrating lymphocytes (TIL), and their sub-fractions co-staining for CD8, FOXP3 and/or PD-1. On the other hand, PDL1 expression was assessed on tumor cells. Statistical analysis was done using JUMP Pro 13 software. Results: There was an induction of membranous PDL1 expression on tumor cells of 70 and 64% in local and metastatic cases respectively. Interestingly, there was a significant number of cases with cytoplasmic expression of PDL1 (46% of local and 36% metastatic cases) in addition to the membranous expression. PD-1 was over-expressed (on ≥ 10% of TIL) in 52% and 68% of local and metastatic cases respectively. FOXP3+ T-cells were abundant in the tumor tissues as 78% of cases had ≥10% of their infiltrating CD3+ T-cells co-staining for nuclear FOXP3. Finally, CD8 were an abundant fraction of total CD3+ infiltrating T-cells in more than 60% and 78% of Local and metastatic cohorts respectively. Correlation of the above studied immune markers with patients clinical outcome shows statistically significant correlation (p = 0.008) between low CD3+ T-cell infiltration in tumor tissues at diagnosis and the relapse of the disease. Conclusions: PDL1 is upregulated, FOXP3+ T-regs are abundant, only the low intensity of CD3+ lymphocytes could predict for higher chances of relapse. These preliminary profiling data provide the basis for future immunotherapy trials for NPC in KFSH&RC