bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocyte apoptosis as a predictive biomarker for radiotherapy de-intensification in EBV-associated nasopharynx cancer.
Authors: Chua Kevin Lee Min , Shihabuddeen Waseem Ahamed , Shwe Than Than , Tan Sze Huey , Wee Joseph , Tan Terence , Chua Melvin 
Published: September 2018

e17545 Background: Emerging evidence in viral-associated head and neck cancers supports the concept of dose de-intensification in these radiosensitive tumors, but different strategies exist in selecting patients for treatment de-intensification. We hypothesize that patients who develop severe late toxicities (LT) to radiation (RT) have better tumor control, due to a common radiosensitivity index. Here, we investigate the utility of a normal tissue radiosensitivity assay (RT-induced lymphocyte apoptosis, RILA) in predicting clinical outcomes (tumor control and normal tissue toxicity) of patients with EBV-associated nasopharynx cancer (NPC). Methods: RILA assay was assessed in a cohort of locally advanced NPC patients from a randomized controlled phase III trial (N = 172, NCC0901) of cisplatin-RT with or without induction gemcitabine, carboplatin and paclitaxel. LT was assessed by CTCAE v.2 at the following intervals (2 mo yr 1, 4 mo yr 2, 6 mo yr 3-5, annually thereafter). We performed the RILA assay (48 h post 8 Gy) in a subset of cases (N = 87). Results: At a median follow-up of 5.7y, DFS (3y 74.9% GCP vs 67.4% Control, p = 0.362) and incidence of severe Grade ≥3 LT did not differ between the treatment arms. In keeping with our hypothesis, onset of severe LT was associated with reduced risk of disease relapse; OR 0.19 (95% CI = 0.02 – 1.59, p = 0.168). High %RILA, stratified by top quartile, was associated with severe LT (OR 1.92 [95% CI = 0.67-5.5], p = 0.26); and lower rate of recurrence (4.5% (1/22), high %RILA vs19.7% (12/61), low %RILA, p = 0.086). Interestingly, subset analyses revealed that CD8+, but not CD4+ subpopulation of immune cells, was strongly associated with recurrence; OR 8.58 for low %CD8-RILA (p = 0.001). Conclusions: Herein, we showed that %RILA may be a useful biomarker for tumor and normal tissue radiosensitivity of EBV-associated NPC. If validated, this predictive assay will enable precision matching of RT-sensitive patients for de-intensification in EBV- and other viral-associated head and neck cancers. The association between tumor control and CD8-subset of immune cells suggests an immune dependency for RT.
Phase II trial of valproic acid combined with cisplatin-based chemoradiation in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) patients (pts).
Authors: Mak Milena Perez , Pasini Fatima Solange , Diao Lixia , Garcia Fabyane Oliveira Teixeira , Takahashi Tiago Kenji , Amadio Alex Vitorio , Siqueira Sheila Aparecida Coelho , Sichero Laura , Snitcovsky Igor M. L. , Kulcsar Marco Aurelio Vamondes , Wang Jing , Castro Gilberto 
Published: September 2018

e17546 Background: Cisplatin-based chemoradiation (CRT) offers LA HNSCC pts a high local control rate, however, relapses are frequent. Here we evaluated if epigenetic regulation by VA, a histone deacetylase inhibitor (HDACi), combined with CRT in LA HNSCC improves response rate (RR). Methods: Patients with unresectable oropharynx (OP) and oral cavity LA HNSCC were included in this Simon two-stage phase II trial. After two weeks of VA (P1), CRT was initiated. Primary goal was RR at 8 weeks after CRT+VA (P2) by RECIST v 1.1. 8/20 and 25/32 responses were needed in the first and second stages for the trial to be considered positive (α = 0.05, β = 0.2). MicroRNA (miR) PCR-array profiling in plasma samples at baseline, P1 and P2, was compared to healthy controls by two sample t-test for each miR. Distribution of p-values was analyzed by beta-uniform mixture. HDAC2 and HR23B tumor immunohistochemistry were also evaluated. Results: Ten LA p16 negative OP pts were included. High-risk HPV was detected in 3 pts samples. Median age was 55 years (41-65). All pts were male, smokers or ex-smokers and with previous moderate/high alcohol intake. Due to significant toxicities seen in an interim safety analysis, accrual was terminated. A RR of 88% was achieved in 9 evaluable pts. A total of 169 miRs were differently expressed among pts and controls (FDR 0.05), including lower expression of known tumor suppressors (TS) such as miR-31, -222, -let-7b and -145. There were no significant differences in the pattern of miR expression at P1 vs. baseline. P2 vs. baseline had lower levels of miR-31, particularly in responders (p 0.007). TCGA HNSCC pts with low levels of miR-31 had a trend towards higher relapse free survival (HR 1.11, 95% CI 0.99-1.25; p = 0.073). Non-responders had no difference in miR expression between baseline and P2. HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease free survival. Conclusions: Although improved RR was seen with VA+CRT, prohibitive toxicities prevented the trial from continuing. Cancer pts and controls had distinct pattern of miR expression, mainly with low levels of TS targeting TP53. miR-31 deregulation in HNSCC needs to be further elucidated. Clinical trial information: NCT01695122.
Prediction model for cervical lymph node metastasis using CT characteristics in patients with head and neck squamous cell carcinoma.
Authors: Choi Young Jun , Chung Mi Sun , Lee Jeong Hyun 
Published: September 2018

e17547 Background: Lymph node metastasis is a major prognostic determinant for patients with head and neck squamous cell cancer (HNSCC). This study aimed to construct a predictive model using CT characteristics of lymph node and tumor for patients with HNSCC to stratify the risk of lymph node metastasis. Methods: The study population was obtained from historical cohort of 472 cervical lymph nodes from 191 patients with HNSCC in a tertiary referral hospital. We analyzed preoperative CT images of lymph nodes according to diameter, ratio of long-to-short axis diameter, necrosis or cystic change, conglomeration, infiltration to adjacent soft tissue, and laterality (ipsilateral vs contralateral) and analyzed T stage. Reference standard was surgical pathologic results. Multivariate logistic regression analysis was performed to predict whether nodules were diagnosed as metastasis or benign. Results: CT features of lymph nodes, including minimal axial diameter, ratio of long-to-short axis diameter, necrosis or cystic change, and T stage were selected as predictors for lymph nodes metastasis. A 10-point risk scoring system was developed, and the risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increases in risk scores. The areas under the receiver operating characteristic curve of the development and validation sets were 0.886 and 0.879, respectively. Conclusions: We have devised a simple predictive model using the CT characteristics of lymph nodes and tumor for HNSCC to stratify the risk of cervical lymph node metastasis. [Table: see text]
Immune-related saliva micro-RNA’s to predict clinical response to a combination of cetuximab and low-dose chemotherapy in head and neck cancer (HNSCC) patients (pts) with poor performance status (PS).
Authors: Bonomi Marcelo Raul , Ado Safoa , Kooshki Mitra , Ahmed Tamjeed , Sullivan Christopher , Waltonen Joshua , Triozzi Pierre 
Published: September 2018

e17548 Background: Recurrent/Metastatic HNSCC is an immunosuppressive disease, especially in the group of patients with poor performance status. Recent studies have shown that low dose chemotherapy, which is much better tolerated than full dose cytotoxic chemotherapy, can increase the anti-tumor immune response and cause tumor regression. In this study we assessed the immune-effects of weekly cetuximab in combination with low dose weekly chemotherapy in HNSCC pts with poor PS by measuring saliva and plasma immune modulatory micro RNAs (miRs). Methods: Patients with recurrent/metastatic HNC with an ECOG PS of 2 or 3 were treated with low-dose weekly carboplatin (AUC 1) and paclitaxel (25 mg/m2) along with weekly cetuximab (400mg/m2 followed by 250 mg/m2). Seven immune modulatory miRs (146a, 155, 181, 20a, 223, 335, 125b) were measured in the saliva and plasma by quantitative PCR prior to treatment and at week 5. Results: Between 4/2016 and 1/2017, 30 patients were enrolled in this study. 24 patients were evaluable for response. Mean age was 69 years (range 51-89), Male/Female: 14/8. ECOG PS 2/3: 13/9. Site of disease: oral cavity 7, pharynx 9, larynx 4, para-nasal 2, unknown 2. Treatment was well tolerated. The most common dose limiting toxicity was skin rash in 10/24 pts (41.5%). Response: partial response 12 (50%); stable disease 4 (16.5%); progressive disease 8 (33.5%). Reduction in miR levels by week 5 were associated with clinical response. Reduction in saliva levels of miRs 146a and 181 correlated with clinical benefit (PR+SD). Pre-treatment saliva levels of miR 146a also showed to be a predictor of tumor response to therapy. Plasma levels of the immune modulatory miRs tested were not associated with response to therapy. Conclusions: The combination of cetuximab and low-dose chemotherapy is active and well tolerated in HNSCC patients with poor PS. Reduction in saliva levels of immune modulatory miRs 146a and 181 were associated with clinical benefit to therapy.
Effect of cetuximab on development of viral infectious complications in laryngeal cancer.
Authors: Vladimirova Liubov Yu , Zykova Tatiana , Ryadinskaya Ludmila A. , Engibaryan Marina , Storozhakova Anna E , Abramova Natalya A , Popova Irina L , Tikhanovskaya Natalya Mikhailovna , Agieva Aza , Pustovaya Irina Viktorovna , Ulianova Yulia 
Published: September 2018

e17578 Background: Cytostatic treatment was shown to influence significantly reactivation of latent viral infections. Our purpose was to study the possible effect of cetuximab on activation of herpesvirus infections. Methods: The blood serum of patients with histologically confirmed laryngeal squamous cell carcinoma was studied before and after chemotherapy. The main group included 9 pts receiving cetuximab+cisplatin+5-fluorouracil, the control group – 9 pts, cisplatin+5-fluorouracil. Antibodies (AB) against viral proteins were detected by ELISA. Results: 6 (66.7%) pts of the main group had primary advanced cancer, 3 (33.7%) – recurrent laryngeal cancer; in control group - 7 (77.7%) and 2 (22.2%), respectively. All pts in both groups were seropositive for HSV 1,2, CMV and EBV before chemotherapy; 4 (44.4%) pts in main group and 7 (77.8%) controls were HPV 6 seropositive. Serological markers of activation of herpes virus infection (IgM or IgG against early viral proteins) after chemotherapy were detected in the main group in 8 (88.9%): HSV 1,2 - 5 (55.6%), CMV - 2 (22.2%), EBV - 3 (33.3%). HSV 1,2, CMV and EBV infections in the control group were activated equally often and found in 3 (33.3%) pts. Clinical signs of herpes virus infection were not observed in either group. A sharp decline in AB titers, sometimes up to their complete disappearance, was registered in 3 (33.3%) pts in the main group and in 6 (66.7%) controls. 1 pt of the main group showed a decline in EBV AB titers and absence of HPV 6 AB titers, 1 pt - a decline in CMV and EBV AB, 1 pt - a decline in HSV 1,2, CMV and EBV AB and absence of HPV 6 AB titers. 2 pts of the control group showed a decrease in HPV 6 AB, 2 pts – their absence, 2 pts – absence of HPV 6 AB and a decline in HSV 1,2, CMV and EBV AB. It could be associated with a greater degree of bone marrow hematopoiesis inhibition during cytostatic therapy. Lymphopenia was registered in the control group more frequently than in the main one. Conclusions: Cetuximab inclusion into chemotherapy does not have an additional negative impact on the development of viral infectious complications. A higher rate of registration of specific antibodies typical of the acute infection phase in the cetuximab group could indicate an adequate response to viral infection.
Changes in blood parameters of patients with laryngeal squamous cell carcinoma during polychemotherapy with cetuximab.
Authors: Vladimirova Liubov Yu , Guskova Nailya , Ryadinskaya Ludmila A. , Engibaryan Marina , Donskaya Aliya K. , Guskova Ekaterina , Gusareva Marina A. , Golomeeva Nadezhda , Abakumova Svetlana V. , Tselishcheva Irina V. , Avanesova Kristina , Nozdricheva Anastasia , Zakharchenko Viktoria , Belgova Svetlana V. , Gornostaeva Ekaterina 
Published: September 2018

e17579 Background: Our purpose was to evaluate changes in blood parameters in patients with laryngeal squamous cell carcinoma (LSCC) during polychemotherapy (PCT) with cetuximab. Methods: Levels of white blood cells (WBC), immature granulocytes (IG) and neutrophils (Ne), as well as levels of C-reactive protein (CRP), lactate dehydrogenase (LDH) and creatinine were studied in the blood of 20 patients with stage I-III LSCC before therapy with cetuximab/cisplatin+5-fluorouracil and on days 2, 9 and 16 of the therapy. The control group (21 patients) received similar PCT without cetuximab. Treatment was assessed using the RECIST criteria. Results: Partial response was observed in 16 (80%) patients of the main group and in 5 (23.8%) controls, stabilization - 4 (20%) and 12 (57.4%), respectively, progression – in 4 (19%) patients of the control group. Patients of the main group with treatment effect showed WBC increase by 2 times after every cetuximab injection (days 2, 9, 16) compared with the initial levels due to Ne and IG increase by 2.7 and 4 times, respectively. WBC and IG levels measured on days 2, 9 and 16 were 13.40±2.86×109/L, 13.52±1.88×109/L, 12.25±2.08×109/L and 0.044±0.021×109/L, 0.056±0.015×109/L, 0.060±0.008×109/L, respectively (p < 0.001). A transient increase in the indexes was replaced by their decrease to the initial values, with the values similar to the reference ones by the end of the treatment. At the same time, we observed decrease in CRP and creatinine levels up to the reference levels (7.69±3.28 mg/L and 74.75±6.54 umol/L, respectively); LDH did not increase. Stabilization was characterized by unchanged WBC levels, positive dynamics of IG and slow decline of CRP level exceeding the reference one (10.0 mg/L) by the treatment end. Reduction of WBC and increase in IG and CRP levels were noted in the controls regardless of the PCT results which could be explained by severity of intoxication syndrome, partially due to the disease and partially due to PCT toxicity. Conclusions: A dual transient increase in WBC and IG levels, reduction of CRP and creatinine during the treatment and unchanged LDH indicate minimization of myelotoxic and general toxic effects of PCT in combination with cetuximab.
A new combination therapy using recombinant human adenovirus p53 injection (rAd-p53) to manage advanced thyroid cancer.
Authors: Zhu Jingqiang 
Published: September 2018

e17585 Background: Although most thyroid cancers have good clinical outcomes, there still have some advanced and radioiodine-resistant thyroid cancers being lack of effective treatment. In this study, we reported a new combination therapy including recombinant adenovirus-p53 (rAd-p53) to treat advanced thyroid cancers. Methods: Two types of unresectable cancers (one advanced PTC and one ATC) received preoperative intratumoral injection of rAd-p53 combined with radiotherapy to shrink the tumor and surgery to remove the tumor. In the matched controlled clinical trial, 82 advanced PTC patients accorded with the inclusive criteria and exclusion criteria were included and matched into experimental group (EG, n = 41) and control group (CG, n = 41). Compared CG received surgery only, EG received preoperative intratumoral injection of 2×1012rAd-p53 viral particles (VP) per 3 days for 5 times and surgery. Results: In the advanced PTC case, the combination treatments including rAd-p53 gene therapy combined with radiotherapy evidently shrunk the tumor and improved the operative condition. Finally, the patient received a successful surgery to remove the tumor totally. In the ATC case, rAd-p53combined radiotherapy obvious relieved enlargement of the lump in the neck and shrunk the tumor. More importantly, the program of surgery to excise the tumor was deemed suitable for this ATC patient through a series of treatments and severity evaluation. In the matched controlled clinical study, compared the control group (CG), rAd-p53 significantly increased the radically operative rate in experiment group (EG) (92.7% vs73.2 %, P= 0.021, n = 41). The 7 years follow-up data showed rAd-p53 decreased locoregional recurrence rate (19.51% vs 36.59%) and new metastasis rate (7.32% vs 17.07%) and increased the median time to locoregional recurrence (24.5 M vs 23.27 M) and new metastasis (19.0 M vs 9.2 M) and the disease-free survival rate (75.61% vs 46.34%) for patients in EG. Conclusions: The combination therapy improved the prognosis to patients with advanced thyroid cancer, indicating this combination therapy including rAd-p53 has an important implication for managing advanced thyroid cancer.
The value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in salivary gland tumors.
Authors: Yucel Idris , Kemal Ozgur , Kemal Yasemin , Bel Ayse , Yildirim Ugur , Atmaca Sinan , Koyuncu Mehmet , Unal Recep 
Published: September 2018

e17592 Background: Salivary gland tumors are rare, comprising only 6 to 8 percent of head and neck neoplasms. Most of them are benign and commonly occur in the parotid gland. In the last decade elevated hematological inflammatory parameters like neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were identified as predictive and prognostic factors in various malignancies. The aim of this study was to evaluate the differences of preoperative of NLR and PLR levels in benign and malignant causes of salivary gland tumors. Methods: This retrospective study was made of a total of 133 patients with salivary gland tumors (age range: 17-89 years; 68 male and 65 female) who were treated between January 2006 and May 2016. Preoperative counts and levels of hematological parameters were obtained from the recorded computerized database in benign and malignant tumors. Results: NLR and PLR levels were significantly higher in the malignant salivary gland tumor group than the benign group( NLR: 0.66±1.3 vs 0.59±0.31 p=0.001, PLR: 160.3±85.7 vs 124.6±44.1 p=0.014). Conclusions: The results of the current study revealed the potential predicitve role of NLR and PLR in patients with salivary gland tumors. These cheap and easily available blood count parameters could be useful biomarkers in the future; but further investigations are needed to confirm our findings. [Table: see text]
Tissue sampling for genomic testing in a community-based center.
Authors: Farhangfar Carol J. , Farhangfar Farhang , Schneider Meghan , Mileham Kathryn Finch , Livasy Chad , Ahrens Will , Kim Edward S. 
Published: September 2018

e18000 Background: Genomic testing requires greater quality than routine clinical diagnostic tests. As genomic testing proliferates and becomes more widespread, adjustments in processes may be needed by community-based pathology, radiology, and surgery groups. Both tissue quality and quantity parameters are essential for successful completion of next-generation sequencing (NGS) panels. Methods: A NGS genomic platform ( > 600 genes) was implemented in a hybrid academic community-based cancer institute, with success/failure rates recorded.. Data were collected from the electronic medical records and biorepository data system. Descriptive statistics assessed success or failure rates by tissue quality or quantity with subgroup analyses by disease sites (primary/metastases), collection procedure, and specimen age. Results: From 6/2015-2/2017, 809 NGS tests yielded 143 (17%) failures [specimen quality (34%) and specimen quantity (66%)]. Of the failed tests, specimens were collected from 26 primary disease sites [lung (21%)] and 18 metastatic sites [liver (29%), lymph node (19%), and lung, omentum, brain, and peritoneal specimens (all < 10%)]. Of the failed tests, all bronchoscopy, EBUS, and peritoneal fluid specimens and the majority of FNAs (78%) were due to insufficient tissue quantity, whereas surgical resection or excision had more issues with quality of the specimen (60%). Of note, surgical specimens ranged from 2005-2016; NGS quality initiatives were implemented system-wide in 2015, leading to substantially fewer failed tests. Cores biopsies had fewer quantity (24%) or quality (18%) issues. The number of tests failing due to insufficient quantity also declined due to education and communication processes implemented. Conclusions: The majority of NGS tests provided valuable information. Implementation of systematic tissue collection (core biopsies) and processing, for primary lung and lung and liver metastases using core biopsies consistently provided the fewest failures and implementing NGS-specific processes improved NGS success rates.
Effect of a new cancer diagnosis on labor force participation (LFP): Has there been a change over time?
Authors: Davidoff Amy J. , Cantley Linda F. , Galusha Deron H. 
Published: September 2018

e18004 Background: Health shocks, such as a new cancer diagnosis, have been shown to reduce LFP in working adults. Over the past decade, there have economic swings, retirement age has increased, while newer cancer treatments may be less toxic or disabling. We update prior estimates of LFP responses, and assess whether patterns changed over time. Methods: Adults from the 1998-2014 waves of the Health and Retirement Study (HRS) who were aged 51+ yrs and working in 1998 or at HRS cohort entry in 2004 or 2010, were followed until their LFP decreased. Decreased LFP was defined as a switch from fulltime work, or a 10 hour or 25% decrease in hours worked. We created time varying indicators for health conditions (cancer, heart condition, lung disease, stroke) newly reported or worsened since the prior wave, condition history, demographics, net worth, and insurance coverage. We estimated discrete Cox proportional hazard survival models for the full sample, and with person-wave observations stratified pre/post 2008. Results: Among 13,918 working adults, mean age was 56 years, 45% women; health history included 5.3% cancer, 9.5% heart condition, 4.1% lung disease, 1.5% stroke; new health conditions included 2.9% cancer, 4.7% heart, 2.3% lung, and 1.3% stroke. Newly reported or worsened cancer, heart and lung disease were associated with similar risk of LFP decrease (see table). Prior history of lung disease, diabetes, arthritis and psychiatric disorders were associated with LFP decreases, but cancer was not. There was no difference in the effect of a new condition on LFP pre/post 2008. Conclusions: Many working adults reported preexisting health conditions. New diagnoses or worsening of cancer and other serious health conditions were associated with LFP reductions, although a longer term history of cancer was not associated with LFP changes. [Table: see text]