bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of reactive gastrostomy tube placement on clinical course of oropharynx cancer patients treated with chemoradiation.
Authors: Dave Ami A , Mozer Marisa A , Zhang Yanyu , Sen Neilayan , Bojko Monica , Huff Amanda A , Al-Khudari Samer , Stenson Kerstin , Fidler Mary J. 
Published: May 2019

e17540 Background: Prophylactic percutaneous gastrostomy tube (PEG) insertion reduces toxicity from chemoradiation to the head and neck but is thought to increase long term feeding tube dependence. This study retrospectively examines incidence and risk factors for treatment related complications of oropharynx cancer patients with and without prophylactic PEGs. Methods: Rush University Medical Center oropharynx cancer patients who received definitive chemoradiation treatment between 2007-2018 were included. Classifications were: “therapeutic” PEG (pretreatment for immediate use due to inability to swallow), prophylactic PEG, reactive PEG (patient/physician preference or 10% weight loss from baseline), and no PEG inserted on treatment. We compared patients with reactive or no PEG to (1) patients with prophylactic PEG, and (2) patients with prophylactic PEG and therapeutic PEG. Multivariate linear and logistical regression models were used to test PEG effect on weight loss, hospital admission, and incidence of acute kidney injury (AKI). Models were adjusted for covariates (age, gender, race, HTN, CAD, DM, other comorbidity). Acute kidney injury (AKI) was creatinine 1.5-2x above baseline. Results: In all, 104 patients were included with mean age 60.1 (SD = 8.65) and baseline BMI 29.6 (SD = 5.62). 53.4% (N = 55) had a prophylactic PEG, 38.8% (N = 40) had reactive or no PEG, 7.8% (N = 8) had a therapeutic PEG. 80 (76.9%) were treated with cisplatin. For all patients, analyses showed that reactive PEG or no PEG patients were more likely to develop AKI during treatment compared to patients with a prophylactic PEG (OR:3.2, p = 0.03), and to patients with prophylactic PEG and therapeutic PEG combined (OR:3.5, p = 0.02). There were no statistically significant differences between PEG groups for weight loss and hospital admission rate. In cisplatin treated patients, reactive PEG or no PEG patients were more likely to be admitted to the hospital compared to prophylactic PEG patients (OR:3.8, p = 0.04). Compared to patients with prophylactic and therapeutic PEG combined, however, there was no statistically significant difference. Patients with reactive or no PEG were more likely to have AKI than prophylactic PEG (OR:5.2, p < 0.01), and as compared to patients with therapeutic or prophylactic PEG (OR:4.4, p = 0.02). Conclusions: Reactive PEGs were associated with increased AKI and hospitalizations compared with prophylactic PEG. With a reactive PEG model, patients may need to have routine lab work and monitoring adjusted to reduce treatment complications.
Evaluating sociodemographic, behavioral and psychologic disparities in 918 head and neck cancer survivors.
Authors: Day Andrew T , Vasudevan Anupama , Wynings Erin , Balachandra Sanjana , Khan Saad A. , Sumer Baran D. , Murphy Caitlin C. 
Published: May 2019

e17541 Background: Minority race, low-income status, tobacco dependence, alcohol abuse, and depression negatively impact overall survival among head and neck cancer (HNC) survivors. Understanding the prevalence and associations of these factors will inform the development of targeted HNC survivorship interventions. Methods: We pooled cross-sectional samples of HNC patients participating in the National Health Interview Survey from 1997-2016. Descriptive statistics were used to compare: 1) HNC survivors to age- and sex-matched adults without cancer (1:4) and 2) behavioral and psychologic conditions in HNC survivors by income status. Results: Mean age of the 918 HNC survivors was 64.8 years and 65.2% were male. Most HNC survivors were non-Hispanic white (85.3%); 7.6% were non-Hispanic black, 4.9% were Hispanic, and 2.2% were of other race and ethnicity. A substantial portion reported income below the poverty threshold (13.9%) and 5.0% consumed > 14 alcoholic drinks per week. Compared to adults without cancer (n = 3,612), a higher proportion (p < 0.05) of HNC survivors (n = 903) exhibited: current tobacco use (21.3% vs 17.4%); serious psychological distress (Kessler-6 score of ≥13; 6.9% vs 3.9%); depressive symptoms most or all of the time (14.1% vs 8.9%). There were particularly striking differences in the prevalence of these factors among HNC survivors by income. Specifically, a higher proportion of HNC survivors with income below the poverty threshold (n = 133) were non-Hispanic black (15.5% vs 5.8%) and exhibited current tobacco use (42.9% vs 18.6%), serious psychological distress (17.4% vs 5.7%) and depressive symptoms most or all of the time (25.3% vs 12.7%) compared to those at or above the poverty threshold (n = 646; all p < 0.05). Conclusions: HNC survivors experience a disproportionate burden of behavioral and psychologic health conditions compared to age- and sex-matched adults without cancer. Low-income status exacerbates these disparities. HNC survivors, especially those in low-income settings, require comprehensive survivorship care targeting these needs.
TCGA data reveal a transcriptomic signature of Sox2 and Nanog targets associated with survival in head and neck cancer.
Authors: Mladkova Nikol , Blakaj Dukagjin 
Published: May 2019

e17546 Background: Head and neck cancers represent a diverse group of tumors linked with HPV infection, alcohol and smoking that contribute to cancer morbidity and mortality globally. Sox2 and Nanog are transcription factors that maintain pluripotency in embryonic stem cells, and their individual expression has been associated with prognosis in head and neck tumors previously. Methods: TCGA dataset containing 522 tumor samples with RNAseq data, clinical information (anatomically classified as 133 oral tongue, 117 laryngeal, 73 oral cavity, 63 floor of mouth, 45 tonsillar, 27 base of tongue and 70 other samples) and 44 normal samples with RNAseq data available was used to detect differentially expressed genes in head and neck tumors. The levels of each gene were then transformed to z-score per patient and classified as over- or under-expressed if those were 2 SD away from the mean. The expression levels were then correlated with survival in individual patients for all tumor combined. Subgroup analysis of oral tongue, laryngeal, oral cavity, floor of mouth, tonsillar cancers was carried out separately. Results: A total of 233 genes were significantly correlated with survival in head and neck tumors ( < 0.01). This geneset was subsequently analyzed for enrichment of common pathway dysregulation or for enrichment of shared regulatory elements. The expression level of a set of a total of 15 genes that represent targets of Nanog and Sox2 was shown to either increase or decrease survival directly dependent on either up- or down-regulated expression levels. Of note, neither Nanog nor Sox2 expression levels individually impacted survival. Subgroup analysis revealed individualized prognostic signatures in each anatomic location, with an overlap of individual genes with Nanog and Sox2 targets signature ranging from 6.25-20%. Conclusions: We describe a prognostic signature in head and neck tumors derived from a TCGA data consisting of genes that represent targets of critical stem cell regulators Sox2 and Nanog. On a subgroup analysis, we also derived prognostic signatures for five anatomic locations and head&neck tumors with various ranges of overlap with Sox2 and Nanog targets signature. Pending validation in additional datasets, those represent an attractive target for further mechanistic evaluation in tumorigenesis in this group of tumors.
Mutational profile of dysplastic lesions evolving to laryngeal cancer.
Authors: Cabezas-Camarero Santiago , García-Barberán Vanesa , Hernanpérez-Hidalgo Diana , Saiz-Pardo-Sanz Melchor , De Pablo Velasco David , Lorca Victor , Iglesias Mari Cruz , Pérez-Segura Pedro 
Published: May 2019

e17551 Background: Few studies have addressed the carcinogenic process of laryngeal cancer from its premalignant phases. Our aim was to compare mutational status of laryngeal dysplasias (LD) evolving to laryngeal cancer (ELC) and not evolving to LC (NELC). Methods: Retrospective study of LD diagnosed between 2007 and 2011. A customized 15-gene NGS panel (DICER, IRF6, NOTCH1, NOTCH2, NOTCH3, NOTCH2NLA, PIK3CA, PTEN, RB1, RIPK4, SYNE1, SYNE2, TP53, TP63, CASP8) was used for mutational analysis with Truseq Custom Amplicon (Illumina) performed in FFPE LD samples and results compared between LD-ELC and LD-NELC. Results: Sixty-four patients (pts) with LD were identified. LD-ELC (N = 23) and LD-NELC (N = 41) were scored as mild (N = 40; NELC: 32 / ELC:8), moderate (N = 8; NELC: 4/ ELC: 4) and severe (N = 16; NELC:5 / ELC: 11). Prior or current moderate-to-heavy tobacco smoking ( > 10 pack-year): 53/64 (83%). Males: N = 50 (ELC: 21; NELC: 29); Female: N = 14 (ELC: 2; NELC: 12). Median time to cancer among 23 LD-ELC: 8 m (range: 0-46). Forty-seven gene variants were detected in ELC not found in NELC, of which 27 were pathogenic/likely pathogenic: Frameshift: 8 (1 in NOTCH2, 1 in PTEN, 2 in RB1, 2 in SYNE1 y 2 in SYNE2); Stop-gained: 3 (1 in NOTCH2NL, 2 in SYNE2); Splicing: 3 (1 in RB1, 1 in RIPK4 y 1 in TP53); Missense: 12 (1 in IRF6, 2 in NOTCH1, 1 in RB1, 2 in RIPK4, 6 in SYNE1). Conclusions: LD from pts ELC showed a different mutational profile than LD-NELC. These results show promise for identifying pts at higher risk for developing LC and should be validated in a larger, prospective study.
Which treatment strategies are the most promising for locally advanced resectable human papillomavirus-associated oropharyngeal cancers?
Authors: Yokota Tomoya , Iida Yoshiyuki , Kamijo Tomoyuki , Morita Kotaro , Mukaigawa Takashi , Nishiya Yukio , Hamaguchi Noriko , Hamauchi Satoshi , Kawai Sadayuki , Onozawa Yusuke , Shirasu Hiromichi , Ogawa Hirofumi , Onoe Tsuyoshi , Nakagawa Masahiro , Onitsuka Tetsuro 
Published: May 2019

e17556 Background: The standard of care for oropharyngeal squamous cell carcinoma (OPSCC) is surgical (S) or non-surgical (NS) approach including chemoradiation (CRT). However, CRT is associated with significant long-term toxicity. Human papillomavirus (HPV) status are associated with improved prognosis for patients (pts) with OPSCC. The aim of this study was to explore the most promising treatment strategy with maintaining survival outcomes while improving QOL for locally advanced resectable HPV-positive OPSCC. Methods: A retrospective analysis of 96 pts with locally advanced resectable HPV-positive OPSCC in Shizuoka Cancer Center between 2004 and 2018 was performed. p16 immunohistochemistry was used to determine HPV tumor status. Clinical characteristics, acute and late toxicities, nutritional support, and survival were compared by treatment modalities. In pts who received S, surgical procedure and histological findings of the surgical specimens were additionally compared between pts who underwent upfront surgery (US) and those who did induction chemotherapy followed by surgery (ICT-S). Results: The median age was 62 years, with the majority having tonsil and base of the tongue as primary site. Thirty-six pts (38%) were current smokers, and 39 (41%) were former smokers. As an initial treatment, 62 (64.6%) and 34 (35.4%) pts underwent S and NS, respectively. Aspiration pneumonia more frequently occurred in NS (41.2%) than in S (8.1%) (p < 0.01). Nutritional support by gastrostomy tube or total parenteral nutrition was required in 20 pts (58.8%) of NS, compared with 15 pts (24.2%) of S (p < 0.01). S showed a trend toward longer overall survival (OS) than NS [HR = 0.204, p = 0.052], while progression free survival (PFS) was comparable between the groups. Of all S, 48 (50.0%) and 14 (14.6%) underwent US and ICT-S, respectively. Transoral surgery was performed in 78.6% of ICT-S, compared with 20.8% of US (p < 0.01). Histological examination of the surgical specimens revealed that positive surgical margins, involvement of ≥ 2 regional lymph nodes, and positive extracapsular extension were present in 7.1, 35.7, and 35.7% of ICT-S, compared with 31.3, 58.3, and 45.8% of US, respectively (N.S.). Pathologic complete response in the primary site and lymph nodes occurred in 43 % of ICT-S. Both OS and PFS was comparable between the groups. Conclusions: Our results suggest the impact of surgical approach on reduced long-term toxicity for HPV-positive OPSCC. ICT followed by surgery might be promising novel treatment strategy.
Outcomes of post-operative treatment with concurrent systemic therapy and radiotherapy (RT) in intermediate (INT) risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.
Authors: Geiger Jessica Lyn , Woody Neil McIver , Tsai C. Jillian , Ghanem Ahmed I. , Dunlap Neal , Liu Howard , Burkey Brian B. , Lamarre Eric , Ku Jamie , Scharpf Joseph , Joshi Nikhil Purushottam , Caudell Jimmy J. , Siddiqui Farzan , Porceddu Sandro , Lee Nancy Y. , Koyfman Shlomo A. , Adelstein David J. 
Published: May 2019

e17567 Background: Patients (pts) with adverse pathologic factors in resected OCSCC excluding positive surgical margins or extranodal extension represent a group of INT risk disease. Though not standard of care, adjuvant CRT is often used in INT pts. We conducted a multi-institutional study to evaluate factors associated with improved outcomes in INT pts treated with or without chemotherapy. Methods: An IRB-approved collaborative database of patients with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by pathologic features and adjuvant therapy. Kaplan Meier curves, log-rank p-values and multivariate analysis (MVA) were used to describe outcomes by treatment including locoregional control (LRC) and disease free survival (DFS). Results: From a total sample size of 1270 patients, 455 INT risk pts were treated with primary surgical resection and adjuvant therapy; 95 received CRT, 274 received RT alone, and 86 received RT without recorded chemotherapy. 49% of pts had perineural invasion (PNI), 24.8% lymphovascular space invasion, 21.5% poorly differentiated histology, 47.3% with pT3/4 disease, and 27.9% with > 2 lymph node positive (LN+). 55.8% of CRT pts were treated with cisplatin. > 2 LN+ was the only significant predictor of LRC (HR 1.49, p= 0.049). PNI and > 2 LN+ were significant predictors of DFS (HR 1.52, p= 0.003 and HR 1.76, p< 0.001). On MVA, after adjusting for > 2 LN+, treatment with cisplatin-RT was borderline significant for LRC (HR 0.52, p= 0.08). 3 year LRC in pts with > 2 LN+ was 84.4% in pts treated with cisplatin-RT compared with 64.9% for RT alone. Conclusions: The addition of cisplatin-based CRT to INT risk pts is controversial but among pts with > 2 LN+ there was a trend toward benefit. This study is limited by small numbers of pts treated with CRT, though these results highlight the need for further investigation in this population to identify INT pts who would benefit from adjuvant therapy intensification.
Diagnostic value of cytokeratin-1, survivin and TG expression in circulating tumor cells in the differentiation of benign and malignant thyroid nodules.
Authors: Liu Jie , Xu Siyuan , Luo Jinghua , Wang Yan , Liu Xia , Du Rong , Tang Yu , Wang Jianwei , Fang Nan , Wu Qixi 
Published: May 2019

e17575 Background: Fine needle aspiration cytology (FNAB) has the advantages of minimal trauma, speed and accuracy, and is currently considered to be the most predictive screening technique before thyroid nodule surgery. However, there are several drawbacks to this method, including certain complications, a relatively high false negative rate, a low acceptance of invasive surgery among patients, and the fact that about 20% of the lesions cannot be clearly defined as benign or malignant. Blood-based noninvasive testing can be used to analyze circulating cancer cells (CTCs) for clinical testing. Here, we investigated the performance of CTCs in thyroid cancer screening. Methods: We established a multi-marker real-time quantitative PCR (CK-19/surviving/Tg) to detect and quantify CTCs in peripheral blood samples. 100 subjects who were diagnosed by ultrasound imaging as having thyroid nodules were enrolled. FNAB or surgical specimens were subjected to pathological tests to differentiate between the benign nodules and thyroid cancer. Meanwhile the CTCs in the blood were isolated and quantified by multi-marker qPCR. Results: Among 100 patients, 50 were diagnosed as Papillary Thyroid Carcinoma (PTC) by pathological test. The sensitivity of each single marker of CK19, Survivin and Tg were only 48%, 44%, and 50% respectively, with the specificity of 94%, 100% and 94%. However, the combination of these three markers results in the highest sensitivity and specificity of 86% and 90%. Thus, the combined marker could achieve the best diagnostic value. Conclusions: Compared with FNAB, CTC is minimally invasive. The performance of the multi-marker real-time quantitative PCR showed that CTC could be used as an adjunctive test after ultrasound evaluation. Our results indicated that CTCs have potential clinical value in the identification of benign and malignant thyroid nodules.
Association between radiotherapy and obstructive sleep apnea in cancer patients: A systematic review and meta-analysis.
Authors: Tawfik Gehad Mohamed , Alshareef Abdulmueti , Mostafa Esraa Mahmoud , Khaled Samar , Hmeda AlMotsim Ben , Abdelwahed Khloud Amr , Amer Ahmed Esmail , Agage Hesham , Emara Nehad Samy , Mahran Saleh Adel , Ebied Amr , Huy Nguyen Tien 
Published: May 2019

e17576 Background: With the increase in survival of cancer patients, consequently, increasing their quality of life is mandatory as well. Sleep disturbances, particularly Obstructive Sleep Apnea (OSA), is one of the main complaints of cancer patients in which patients face frequent episodes of upper airway closure during sleep. Possible causes for OSA include either the specific cancer or its treatment whether sedatives, narcotics, radiotherapy, or chemotherapy, but the primary cause is still hard to prove. Our aim was to investigate the association between the occurrence of OSA and radiotherapy in cancer patients. Methods: On the 9th of September, 2018, we have searched comprehensively 12 electronic databases to retrieve relevant studies. All eligible studies that assess the association between OSA and radiotherapy in cancer patients were included in our meta-analysis. Quality assessment of included studies was done using the NIH tool for cohort and cross-sectional studies. Results: Fourteen studies met our selection criteria, eight studies were eligible for our meta-analysis. There was a positive association between the occurrence of OSA and radiotherapy in cancer patients (OR 1.16, 95% CI [0.52–2.56]; P = 0.718). OSA was noted in 103 of 181 cancer patients who received radiotherapy, yielding a remarkable overall prevalence of 63% (95% CI [0.36–0.85]; P = 0.343). A positive risk ratio for the development of OSA in cancer patients treated with radiotherapy was detected (RRs 1.27, 95% CI [0.81–2.00]; P = 0.297). The overall mean of apnea hypopnea index (AHI) for patients with OSA in six studies was 22.45. Conclusions: These findings point to a striking association between OSA risk and radiotherapy in cancer patients. Since the early recognition and management of OSA in such patients may play an important role in improving their quality of life, we recommend screening all cancer patients treated with radiation for early signs of OSA to further improve their survival.
Next Generation Sequencing in Salivary Gland Carcinomas: Do Actionable Mutations Lead to a Therapeutic Advantage? A Multicenter Experience.
Authors: Moore Assaf , Gutfeld Orit , Billan Salem , Bar Yael , Maurice Dror Corinne , Ospovat Inna , Gordon Noa , Popovitzer Aron 
Published: May 2019

e17582 Background: Salivary gland cancers (SGCs) are rare tumors. The approach to recurrent or metastatic patients is histology dependent, as the clinical course is highly variable. Response rates to chemotherapy are modest and no second-line therapies have proven to be effective. The rarity and heterogeneity of SGCs make conducting clinical trials challenging. Recent reports of Next Generation Sequencing (NGS) in SGCs have identified unique genetic attributes of certain histological classes. However, despite the elaborate work done with genetic characterization, there is very little evidence on whether these findings translate to tumor control. In this study, we aimed to explore the treatment outcomes of patients with advanced SGCs who underwent a commercially available NGS. Methods: A retrospective analysis of all patients with histologically confirmed SGC treated in three major Israeli cancer centers who underwent NGS. Results: Twenty-seven patients were included. Eighteen patients were male (66.6%). The median age was 59 (range 38-81). Histologic type was adenoid cystic carcinoma in 11 (40.7%) patients, 8 (29.6%) mucoepidermoid carcinomas, 5 (18.5%) adenocarcinomas, 2 (7.4%) salivary duct carcinomas and 1 (3.7%) acinic cell carcinoma. Twenty-five (92.6%) had recurrent disease after initial curative treatment and 2 were initially diagnosed with metastatic disease. Median time to recurrence was 24.3 months. The median number of systemic treatment lines was 1 (range 0-5). Thirteen patients (48%) had targetable findings in NGS, including: 5 ERBB2 amplifications, 3 PIK3CA mutation, 1 TRIM33-RET fusion, 1 FGFR3-TACC3 fusion, 1 MSI-high and 2 high mutational burden. Nine patients were treated accordingly; 5 in the second-line and 4 as first-line treatment. Median progression-free survival for targeted treatment was 8.4 months. Of 4 patients who achieved durable responses to anti-RET/HER2 agents and immunotherapy of 8.4 – 31.1 months, two are ongoing. The median overall survival for all patients was 101.75 months, was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (p = 0.26). Conclusions: In the absence of a well-established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGCs.