bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is uterine cancer screening indicated or possible in high risk special populations?
Authors: Lee Susan , Delaveux Anquilla , Crosby Claud , Chen Yiju Amy , Khozaim Kareem , Buenconsejo Lee , Timoteo Ianeta , Matthews Roland , Del Priore Giuseppe 
Published: May 2019

e17126 Background: Uterine cancer (UC) is being considered for screening by the CDC due to its relative ascendancy in incidence. We sought to determine its potential for screening using a vanguard of contemporary cancer risk with high non-communicable disease rates (American Samoa [AS]) as a model sample set, and then Grady Hospital (GH) as a test population for screening. Methods: Public access de-identified databases covering the entire national population of AS over several time periods and de-identified GH tumor registry data. Results: In 2014 AS reported 258 new cancers (9.4/10,000 women/yr) including UC (36%), breast (37.6%), cervix (6.6%), ovary (5.1%), and others (14.7%). UC was the leading cause of gynecologic deaths (1.6x > ovarian or cervical). From 2004 - 14 the incidence of UC increased 78.9% to 3.4 cases/10,000 women/yr while breast cancer increased 52.2% to 3.5 cases/10,000. In the most recent 24 months, UC was 2.5x more likely to be diagnosed than breast, 3.6x more than colon, 8x more than cervical and 10.7x more than ovarian cancers. Gyn cancers were the leading cause of cancer death among women after lung. Based on this high incidence of UC, we sought to determine if it would be possible to reach US patients for potential screening using an urban population with health disparities in a test sample of potential beneficiaries of screening for UC the GH Morehouse service (79% black; mean age 58 (33 - 88). From 2010-6, 197 UCs were treated at GH; 96% were GH patients prior to diagnosis with an average time from earliest hospital encounter to the UC diagnosis of 1.75 years (0 – 5.5). Changes from 1st GH encounter to UC diagnosis and treatment including BMI, age, co-morbidities, etc will be presented. Conclusions: Uterine cancer has similar characteristics to currently screened cancers with an incidence in some high-risk population just under breast and prostate, but ahead of lung and colon. An enriched population, eg. BMI combined with age, especially with disparities, could benefit most from changes in screening strategy and management. Patients with UC are accessible in the hospital of their treatment for potential screening years before diagnosis. This may be an opportunity to reduce cost and morbidity from a rapidly increasing cancer.
A differential response to cetuximab in patients with recurrent unresectable or metastatic head and neck cancer following immunotherapy (IO) exposure: An institutional experience.
Authors: Ali Haythem Y. , Abdel Rahman Zaid , Sheqwara Jawad 
Published: May 2019

e17500 Background: Metastatic head and neck cancer is a diagnosis with poor prognosis and very little in terms of available active therapy. Until recently the mainstay of therapy was chemotherapy with or without cetuximab. The regimen of cetuximab (C), platinum (P) and 5FU has a response rate(RR) of 36% in the first line setting, and a PFS of 5.6 months and OS of 10.1 months. In the setting of post first line therapy immunotherapeutic agents (IO) have average RR of 15% and median OS of 8 months. Methods: We studied all patients with metastatic or recurrent head and neck cancer who were treated with an IO at our institution between May 2016 and July 2018 evaluating their entire history of therapy. 19 patient were treated with IO at our institution in the designated period of whom 9 received nivolumab (N) and 10 received pembrolizumab ( P ). Patients treated on trials were excluded. Patients who received less than 1 cycle of therapy were also excluded. 7 of the 19 patients received an IO in the first line setting after being refractory or resistant to platinum containing definitive therapy, 7 received the IO after a cetuximab (C) containing first line regimen, 1 patient received IO in second line but was naïve to C and 4 received IO in the third line setting. Results: 3 of 19 patients treated with IO had partial response, there were no complete responses, 6 patients had stable disease as their best response and 10 patients progressed at the time of their first evaluation. 11 of 19 patients received additional therapy post IO. 10 patients received taxane based therapy 5 of whom the taxane was combined with C. Of the 5 patients who received a taxane and C combination 2 had CR, 2 had PR and one had PD. Of the 5 who received other taxane regimens, 1 had PR 1 had SD and 1 had PD, 2 expired prior to their first evaluation. The patient who received a non taxane regimen all had progressive disease. Of the 4 responding patients to C regimens 1 had SD during IO therapy and 3 had PD. The longest response duration to a C regimen post IO was 628 days. Conclusions: We observe an unusual response rate among patients treated with a combination of taxanes and cetuximab after IO therapy. This finding may relate to a modifying effect of IO on sensitivity to subsequent therapy. This observation merits further investigation.
Preclinical study of PD-0332991 on EBV-positive NPC cell lines and xenografts.
Authors: Xue Zhichao 
Published: May 2019

e17506 Background: Originated from nasopharynx, nasopharyngeal carcinoma is a subtype of head and neck cancer, which is consistently associated with EBV infection. It is prevalent exclusively in south of China, Malaysia and southeast Asia. Previously, there was only one EBV positive cell line, c666-1, for NPC study, the new EBV positive cell lines and xenografts established by our lab recently represent better models for preclinical drug test. The objective of this preclinical study is to evaluate the therapeutic effect of specific CDK4/6 inhibitor PD-0332991 in our new established EBV positive NPC cell lines and Xenografts. Methods: Cell lines were cultured in both 2D and 3D condition, cytotoxic test was conduct by Resazurin in 2D and by cell titer-glo in 3D. Cell cycle was analyzed by Western blot and flow cytometry. In the animal study, PD-0332991 was first used as single drug administrated to xenograft mice daily by oral gavage. Secondly, SAHA as a HDAC inhibitor was used to combine with PD-0332991 in this study, which was i.p. injected into animal every other day. Tumor size, body weight well as micro-pets scan data was recorded. The data from each experiment was analyzed by ANOVA and unpaired t-test for significant drug responses. Results: PD-0332991 was first identified to be effective during in vitro study. Beside single drug effect, when combination with SAHA, a synergistic effect was observed both in vitro and in vivo. In single drug study, PD-0332991 can significantly inhibit tumor growth in 3 of our xenografts (XENO76: P < 0.0001, XENO32: P < 0.0001, XENO23: P = 0.0019). In combination study, through tumor size and micro-pets scan, combination treatment induced significant decrease in tumor size and tumor metabolism states in animal models compare to vehicle, PD-0332991 and SAHA treatment. Conclusions: PD-0332991 is identified to be effective in our preclinical test by using our new established EBV positive cell lines and xenografts, this could be a promising treatment for NPC patients after clinical trial.
Use of prophylactic percutaneous endoscopic gastrostomy (pPEG) tube in head and neck cancer (HNC) patients and correlation of weight loss with treatment interruptions.
Authors: Pandey Deepali , Gibbs Lisa , Sahu Kamal Kant , Siddiqui Ahmad Daniyal 
Published: May 2019

e17509 Background: HNC patients are at risk for weight loss which can cause treatment interruptions, and poorer outcomes. There is no consensus on optimal timing of PEG tube placement in HNC patients undergoing concurrent ChemoTherapy (CT) and RadioTherapy (RT). The aim of this study is to determine if pPEG tube would decrease weight loss (WL) in HNC patients. We also analyzed correlation between WL and CT interruptions (CTI), RT interruptions (RTI), and intravenous fluid requirements (IVFr). Methods: This is a prospective study. A total of 16 HNC patients undergoing concurrent CT, RT were included. Before treatment initiation, a PEG tube placement was recommended as a mode of nutrition. 13 patients chose to get pPEG tube and 3 refused. We collected data on weight at 0 and 2 months, CTI, RTI, and IVFr. CTI included missed as well as reduced chemotherapy doses. RTI included missed radiations. Statistical tests used - t-test, Levene’s test for equality of variances and point biserial correlation. Results: Median age - 63 years; Gender: 14 Male/2 Female; Tumor location - Oral cavity - 31.3%; Oropharynx - 43.7%; Larynx - 25%; Nasopharynx and Hypopharynx- 0%. Stages were - II (6.2%), III (37.5%) and IV (56.3%). 2 patients were non-smoker and 4 were Human Papilloma Virus positive. Mean WL(lb) in pPEG (n = 11) vs non-PEG (n = 3) group was 10.3 vs 20.3 (p = 0.045, one-tailed t-test). Average percentage of WL: PEG vs non-PEG - 5.8 vs 8.2; RTI vs not - 8.9 vs 5.3; CTI vs not - 6.9 vs 5.8; IVFr vs not - 6.8 vs 4.5 ( > 7.5% WL over 3 months is significant (ADA/ASPEN)). CTI, RTI and IVFr were positively correlated to WL (correlation coefficient: 0.16; 0.32; 0.17 respectively). CTI and RTI in pPEG group were 23.1% and 38.5% respectively. CTI and RTI in non-PEG group were 33.3% and 66.7% respectively. 2 patients in pPEG group had average weight gain of 2.75 lb. Only 3 patients had PEG tube related complications - infections and clogging. Conclusions: pPEG tube decreases weight loss in locally advanced HNC patients. Patients with higher weight loss had more chemoradiation interruptions and IVFr. HNC patients undergoing concurrent CT, RT should be encouraged to maintain weight and get a PEG tube.
Quality of life assessment in dose escalating head and neck radiation therapy.
Authors: Hany Riham H. , Saad Ehab , Al sirafy Samy , Kader Yasser A. , Hassan Aly Mohamed Abdulla , Abdelhady Eman ,   Kasr Al Ainy, Cairo University Hospitals, Cairo, Egypt
Published: May 2019

e17511 Background: Both Dose escalation and acceleration can achieve higher tumor control rates with uncertain role of addition of concurrent chemotherapy. We aimed at developing a protocol for patients unable to receive the standard CCRT with little toxicity profile. Toxicity and Quality of life assessment were our primary end points in this pilot phase II trial. It is known from literature that pre-treatment QOL affects survival. Also, changes in QOL after treatment predict survival in cancer patients. Methods: 63 locally advanced HNC patients were randomized to receive (Arm A) 70Gy/35fr/7wks at 2Gy/fx concurrently with weekly Cisplatin 40mg/m2 or to receive (Arm B) 74Gy/33fx/6.5wks at 2.24Gy/fx with calculation of the Biological equivalent doses. CTCEA v4.3 was used to assess toxicity and Functional Assessment Cancer Therapy-Head & Neck (FACT-H&N) questionnaire (39-item) was used to assess QOL. The Questionnaires were collected and their scorings were calculated to get the FACT-H&N Trial outcome index (TOI), FACT-G and FACT-H&N total score pre-radiotherapy, 3 and 6 months post-radiotherapy for each patient. Results: There were 33 patients in arm A vs. 30 patients in arm B with median follow up 24.2 months. Our results showed statistical significant decrease of chemotherapy related toxicities (nausea, vomiting, neutropenia and anemia), acute (mucositis, oral pain, voice alteration, fatigue and acute dysphagia) and some late toxicities (late xerostomia) in the investigational arm vs. the CCRT arm. Regarding the FACT QOL assessment and scorings of the different parameters, there was no statistical difference between both arms in all FACT-H&N TOI, FACT-G and FACT-H&N total scores at pre-treatment, 3 and 6 months post treatment. Also when analyzing the mean change with time across the two groups pre-radiotherapy, 3 and 6 months post radiotherapy, it was not statistically significant. Our results did not demonstrate any significant differences in 2-year disease local control, PFS and OS between both arms, with comparable patterns of relapse. Conclusions: Slightly dose escalated hypofractionated regimen could be an option in LA-HNC treatment without affecting QOL, which needs confirmation in prospective large multi-centric trials. Clinical trial information: NCT03699969.
Triple combination treatment with anti-EGFR monoclonal antibody, low-dose chemotherapy, and anti-PD1 immune check-point inhibitors for recurrent and/or metastatic head and neck squamous cell carcinoma: A single institute experience.
Authors: Lin Ying-Chu , Uen Wu-Ching , Hao Sheng-Po , Hsiao Chen-Yu , Lai Hung-Chih 
Published: May 2019

e17514 Background: The 1st line treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M SCCHN) was EXTREME regimen established by Vermorken at al since 2008. Recently in ESMO 2018, Keynote-048 presented frontline pembrolizumab monotherapy or combined chemotherapy had a better overall survival than EXTREME regimen, though with poor PFS (3.2m-3.4m) and response rate (19-23%). But chemotherapy plus pembrolizumab showed a shorter duration of response than the pembrolizumab alone. Therefore, role of chemotherapy as a partner of IO is debated. We presented a retrospective report of triple combination treatment of cetuximab, low-dose chemotherapy and anti-PD1 check-point inhibitor for R/M SCCHN patients as a e-publication in ASCO 2018. This is a update report. Methods: We retrospectively reviewed charts of R/M SCCHN patients who started triple combination of cetuximab, low-dose chemotherapy and anti-PD1 therapy during the period of Feb. 2017 till Jan.31 2018. The contents of combinations, previous treatments, duration of combination treatments, best response, and adverse effects were recorded. Data cutoff is Jan.15 2019. Results: Total 15 patients reviewed. The mean age was 55.4 years (age range 32 – 71 years). Previous treatments included chemotherapy (80%), anti-EGFR (33.3%), anti-PD1 check-point inhibitor (53.3%). The median duration of follow up was 434 days (range 187–707 days). Complete response was observed in 3 patients (20%), partial response in 7 patients (46.7%), stable disease in 4 patients (26.6%) and disease progression in 1 (6.6%). Objective response rate(CR+PR) observed was 66.7%. Clinical benefit rate(CR+PR+SD) observed was 93.3% . Dose of Cetuximab was 250-500mg/m2 every 2-3 weeks. Combination of chemotherapy included PF, TP, or docetaxel monotherapy. Doses were Cisplatin 30-50mg/m2, 5-FU 600-1000mg/m2, or docetaxel 20-30mg/m2; all in every 2-3 weeks. Anti-PD1 immune check-point inhibitors included Nivolumab 1-3mg/kg or Pembrolizumab 1-2mg/kg, every 2-3 weeks. Six patients (40%) died: 2 due to progression of disease, 1 due to tumour bleeding, 2 due to pneumonia, and 1 due to fungemia. Conclusions: Our real-world report might suggest a possible role of ADCC effect of cetuximab and less-toxic chemotherapy as a partner of IO. Further prospective study of triple combination therapy with biomarker evaluation is recommended.
Patterns of local extension and nodal involvement from 1300 nasopharyngeal carcinoma patients: An imaging-based predictor of distant metastases.
Authors: Fan Dan , Wang Ying , Tian Yifu , Lee Nancy Y. , Shen Liangfang 
Published: May 2019

e17516 Background: Distant metastasis is a main determinant of prognosis in patients with nasopharyngeal carcinoma(NPC). We explored the patterns of disease spread in NPC patients and identified the pattern correlates with distant metastases. Methods: The imaging documents of 1300 consecutive newly diagnosed nasopharyngeal carcinoma between 2012 and 2016 were reviewed. According to the incidence rates of tumor invasion, the anatomic sites were classified into high-risk group (≥50%), medium-risk group (≥10%~ < 50%) and low-risk group ( < 10%). The location of lymph nodes was determined by 2013 updated guidelines for neck node levels. Additionally, we developed a novel classification based on tumor spreading patterns, as shown in Table. Moreover, we validated the prognostic accuracy of the classification in a validation cohort from a different institution, 241 non-metastatic NPC patients were retrospectively enrolled. Kaplan-Meier method and log-rank test were used to analyze all time-to-event data. Results: The incidence rates of tumor invasion were 0.2% ~91.2%, 95.2% cases across the midline. If anatomic sites in high-risk group or median-risk group were involved, the incidence rates in adjacent medium-risk sites or low-risk group were increased. On the contrary, the incidence rates were decreased when the adjacent high-risk sites or median-risk group were not involved. 85.9% cases had involved lymph nodes. Only 3.9% had skip metastases. The incidence rates of nodal involvement were increased when adjacent upper nodal level was involved. In validation cohort, distant metastases were present in 32/241 NPC patients (13.3%) and 3-year distant metastasis-free survival(DMFS) in local, superior, inferior, and mixed type were 95.0%, 91.3%, 89.0%, and 78.7%, respectively. Cumulative survival curves for former three patterns were relatively similar and were clearly separated from mixed type. DMFS was significantly lower for patients with mixed type pattern than for those with other patterns(P = 0.018). Conclusions: Local disease in NPC patients spreads stepwise from proximal sites to more distal sites. The frequency of metastases in the jugular lymph node chains decreased in the cranio-caudal direction. Based on the patterns of tumor extension, an imaging-based predictor of distant metastases was developed and may be used as a prognostic marker for selecting patients to further systemic treatments. [Table: see text]
QOL assessment in head and neck cancer patients undergoing neoadjuvant chemotherapy and its impact on overall survival.
Authors: Dhumal Sachin , Patil Vijay Maruti , Noronha Vanita , Joshi Amit , Bhattacharjee Atanu , Roy Somnath , Das Sudeep , Prabhash Kumar 
Published: May 2019

e17519 Background: NACT (neoadjuvant chemotherapy) is one of the treatment options in advanced head and neck cancer (H&N cancer); however there is limited quality of life data available in these patients. Methods: Between August 2013- April 2014, 90 technically unresectable H&N cancer patients who were underwent NACT at our centre were selected for this analysis. EORTC QLQ-C30 and HN35 version 3.0 was used for quality of life assessment at baseline and after 02 cycles of NACT. PFS and OS was estimated by Kaplan Meier method. The mean change in QOL at various domains was calculated with 95% CI. The relationship between change in QOL domain and OS was analysed. Results: The median age of the cohort was 45 years (Range 21-65 years). The predominant subsite was oral cavity, in 62 patients (68.9%).The median PFS and OS was 10.53 months (95%CI 8.1-13.0) and 20.8 months (95%CI 15.1-26.5). The mean scores for all domains of QOL are shown in table 1. Conclusions: NACT leads to improvement in QOL in patients treated with head and neck cancers and its has impact on OS.[Table: see text]
Biomarkers of resistance to cetuximab in head and neck squamous cell carcinoma (HNSCC).
Authors: Surikova Ekaterina I. , Kit Oleg I. , Neskubina Irina V. , Frantsiyants Elena M. , Vladimirova Liubov Yu , Lyanova Aza A. , Engibaryan Marina A. , Shalashnaya Elena V. , Aedinova Irina V. , Ulianova Yulia V. , Volkova Viktoriya L. , Pustovaya Irina Viktorovna , Ezhova Maria 
Published: May 2019

e17523 Background: Treatment of advanced HNSCC (T3 and T4) involves the use of anti-EGFR monoclonal antibodies targeting the EGF-EGFR and VEGF-VEGFR cascades responsible for the cell proliferation, differentiation, invasion, metastasis, angiogenesis and apoptosis. The purpose of the study was the search for biomarkers of resistance to cetuximab in HNSCC patients. Methods: Tumor biopsy was performed in patients with HNSCC (n = 40) (Т3-4N0-1M0) before and after two cycles of chemotherapy with cetuximab - 400 mg/m2 administered on day 1 and 250 mg/m2 per week, cisplatin 100 mg/m2 on day 1, fluorouracil 1000 mg/m2 - 96-hour continuous infusion. Patients were divided into group 1 (progression, n = 11) and group 2 (stabilization and partial remission, n = 29). Levels of VEGF-A (pg/mL) (BenderMedSystem, Austria) and TGF-β (pg/mL) (eBioscience, USA) were determined in biopsy samples by ELISA, and the VEGF-A/TGF-β ratio was calculated. Statistical analysis of the results was performed using the Statistica 10.0 program with M±m determination. Differences were considered significant at p < 0.05. Results: Before treatment, levels of VEGF-A in biopsy samples were 634.8±37.2, TGF-β – 1092.5±71.9, and VEGF-A/TGF-β – 0.58±0.03. After 2 cycles of chemotherapy with cetuximab, results in group 1 for VEGF-A were 680.3±41.2, TGF-β – 1773.7±111.4, and VEGF-A/TGF-β – 0.384±0.021; in group 2: VEGF-A – 487.7±26.1, TGF-β – 572.3±34.7, and VEGF-A/TGF-β – 0.85±0.043. Thus, after 2 cycles of chemotherapy with cetuximab, TGF-β in group 1 increased by 1.6 times and VEGF-A/TGF-β – by 1.5 times (p < 0.05). In group 2, VEGF-A decreased by 1.3 times, TGF-β by 1.9 times, and VEGF-A/TGF-β increased by 1.46 times (p < 0.05). Conclusions: Decreased levels of markers and increased VEGF-A/TGF-β can predict cetuximab efficacy. Increased TGF-β and reduced VEGF-A/TGF-β allow predicting resistance to chemotherapy with cetuximab.
Changes in KRAS mutations in patients with oral mucosa and tongue cancer (OMTC) undergoing medical treatment with cetuximab (Cet).
Authors: Lyanova Aza A. , Kit Oleg I. , Enin Yaroslav S. , Timoshkina Natalya N. , Engibaryan Marina A. , Aedinova Irina V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Chertova Natalia A. , Vladimirova Liubov Yu 
Published: May 2019

e17524 Background: Mutations in KRAS are known to be predictors of anti-EGFR therapy efficacy. Besides the mutation status of the treatment-naive tumors the changes in the level of mutant DNA during medical treatment are also of clinical interest for the individualization of the treatment. The purpose of the study was to detect somatic single nucleotide polymorphism (SNP) activating mutations in KRAS exon 2 in patients (pts) with OMTC undergoing chemotherapy (CT)±Cetuximab (Cet). Methods: Extracellular DNA samples were obtained from plasma of pts with OMTC (T3-4No-1Mo) undergoing CT (CDDP+5FU)+Cet (group A) before treatment and in 2 weeks after. Patients undergoing CT (CDDP+5FU, no Cet) were included in Group B. 7 activating mutations in KRAS exon 2 were detected by Droplet Digital PCR method (DD PCR) with "KRAS Screening Multiplex Kit" (BioRad, USA). Results: Samples from 28 pts were included. The frequency of SNP activating in KRAS exon 2 before treatment was 25%. In the group A (n = 12) KRAS mutations were not found or the level of mutant DNA did not exceed 1%. No significant changes were found in this group after treatment. The group B (n = 16) had some KRAS variations the majority of which did not change after treatment. However, 2 pts had a sharp increase in mutant DNA: from 0.03% before CT in both cases to 17.04% and 56.38% -after treatment (p < 0.01). Conclusions: Medical treatment, especially CT, could cause the changes in activating mutations in KRAS exon 2 in pts with OMTC. Revealing of these changes is of great importance for the following treatment options. Detection of mutant extracellular DNA by DD PCR could be valuable to monitor their status during the treatment.