bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of treatment patterns and prognosis in correlation with age in patients with vulvar cancer: A subset analysis of the AGO-CaRE-1 study.
Authors: Prieske Katharina , Woelber Linn Lena , Muallem Mustafa Zelal , Eulenburg Christine , Jueckstock Julia Kathrin , Hilpert Felix , de Gregorio Nikolaus , Iborra Severine , Ignatov Atanas , Hillemanns Peter , Fuerst Sophie , Strauss Hans-Georg , Baumann Klaus , Thiel Falk , Mustea Alexander , Meier Werner , Harter Philipp , Wimberger Pauline , Sehouli Jalid , Mahner Sven 
Published: May 2020

6090 Background: Despite an increasing incidence with simultaneous decreasing age of onset, the impact of age on prognosis and treatment patterns in primary squamous cell vulvar cancer (VSCC) has not extensively been studied yet. Methods: This is a subgroup analysis of the AGO-CaRE-1 study. Patients (pts) with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998-2008, were included in a centralized database (n = 1618). In this subgroup analysis pts were analyzed according to age ( < 50yrs (n = 220), 50–69yrs (n = 506), ≥70yrs (n = 521)) with regard to treatment patterns and prognosis. Only pts with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. Results: At first diagnosis, women ≥70yrs presented with more advanced tumor stages ( < 0.001), larger tumor diameter ( < 0.001), poorer ECOG status ( < 0.001), higher tumor grading (0.048), as well as a higher rate of nodal involvement ( < 0.001). Older women ≥70yrs showed more commonly HPV negative tumors compared to the other age groups (54% vs. 36.5% in < 50yrs vs. 47.9% in 50-69yrs, p = 0.03). Disease recurrence occurred significantly more often in elderly women (48% vs. 21% in < 50yrs vs. 37.4% in 50-69yrs, p = 0.001). Particularly isolated vulvar recurrence was more frequent in the elderly in comparison to the younger groups (18.2% vs. 15.2% in 50-69yrs vs. 12.7% in < 50yrs, p = 0.001). Age was an independent prognostic factor for disease-free survival (DFS) (HR: 1.7, 95%CI: 1.24-2.46, p = 0.001) with 2-year DFS being 81.1% (< 50yrs), 65.8% (50–69yrs), and 59.3% (≥70yrs), respectively. Elderly women (age group ≥70) had a 221% higher risk for death or recurrence, compared to the youngest group (HR: 3.21, p < 0.001). In a multivariate analysis ECOG, tumor stage, grading, and receipt of (chemo)radiation were further independent prognostic factors for recurrence. Conclusions: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year PFS in comparison to younger pts groups. Potential reasons for delayed time of diagnosis could be self-awareness and/or more aggressive tumor biology due to HPV negative disease.
A prospective phase II open-label randomized controlled trial to compare mandibular preservation in upfront surgery to neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer.
Authors: Chaukar D. , Pai P. S. , Chaturvedi Pankaj , Pantvaidya Gouri , Deshmukh Anuja , Nair Deepa , Thiagarajan Shivakumar , D'Cruz Anil , Prabash Kumar , Noronha Vanita , Patil Vijay Maruti , Laskar Sarbani 
Published: May 2020

6518 Background: The study objective was to evaluate the non-Inferiority of survival and ability to preserve mandible with the use of neoadjuvant chemotherapy (NACT) in locally advanced oral cancers compared to upfront surgery alone without compromising survival. Methods: This study was a randomized, single centre, non-inferiority trial. Eligibility criteria included treatment naïve histologically confirmed cancer of the oral cavity; cancers requiring segmental resection for paramandibular disease without clinicoradiological evidence of bone erosion, clinical T2, T3 and T4, any N, M0 as per TNM (AJCC) 7th edition, age at least 18 years; and written informed consent. The patients were randomly assigned (1:1) to receive either upfront surgery followed by adjuvant treatment (Standard arm-SA) or receive two cycles of three drugs NACT (Docetaxel, Cisplatin, 5-Flurouracil) at three weekly interval (Intervention arm-IA). Depending on the response after two cycles, the patient would either receive an additional third cycle or undergo surgery followed by adjuvant treatment as decided by the tumour board. The primary endpoint was mandible preservation rate at 30% in the experimental arm. The secondary end points being Loco regional control and treatment related toxicity. Results: Between September 2010 and April 2013, 68 patients were enrolled and randomized to SA (34 patients) and IA (34 patients) with a median follow-up of 3.6 years (IQR 0.95- 7.05 years). Majority of the patients were T4 (n = 40, 58.8%) In the IA 28 patients had partial response (n = 28,82.4%), with a mandible preservation (Marginal Mandibulectomy) rate of 48% (n = 16/34). There were no close or positive margins in the IA. All patients received adjuvant treatment. The number of recurrences was similar in both the arms. All patients in the IA developed toxicities with the majority developing Grade III-IV toxicities (Grade III: 14, 41.2%, Grade IV: 11, 32.4%) (p = 0.739). The disease free survival (DFS) (p = 0.715, HR 0.911[0.516-1.607]) and overall survival (OS) (p = 0.747, HR 0.899[0.510-1.587]) were similar in both the arms. Conclusions: NACT seems to be a feasible option for mandibular preservation with acceptable toxicities in a select group of patients without compromising survival. However this needs to be tested in a larger phase III randomized trial. Clinical trial information: CTRI/2015/11/006396 .
Development and validation of a gene expression-based signature predicting efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A multicenter cohort study.
Authors: Lei Yuan , Li Ying-Qin , Jiang Wei , Hong Xiao-Hong , Ge Wen-Xiu , Zhang Yuan , Hu Weihan , Wang Ya-Qin , Liang Ye-Lin , Li Jun-Yan , Chen Lei , Xie Fangyun , Li Wen-Fei , Mao Yan-Ping , Liu Xu , Chen Yu-Pei , Tang Ling-Long , Sun Ying , Liu Na , Ma Jun 
Published: May 2020

6522 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene expression signature that can identify patients who will benefit from IC. Methods: We screened chemoresistance-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemoresistance-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Results: We identified 43 chemoresistance-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] 0.87, sensitivity = 87.5%, specificity = 75.6%). We then apply the 6-gene signature to classify patients into the benefit group and the no-benefit group. In the benefit group, patients could benefit from IC in terms of failure-free survival (hazard ratio [HR] 0.54 [95% confidence interval 0.34-0.87]; p = 0.01), while patients in the no-benefit group could not (HR 1.25 [95%CI 0.62-2.51]; p = 0.53). In the clinical trial cohort, the developed 6-gene signature was also highly accurate at predicting the response to IC (AUC = 0.82; sensitivity = 87.5%; specificity = 71.8%). Additionally, IC conferred failure-free survival benefits only on patients in the benefit group (HR 0.37 [95%CI 0.18-0.75], p = 0.004) and not on those in the no-benefit group (HR 0.70 [95%CI 0.27-1.82]; p = 0.46). In the external independent cohort, similar results were observed. Conclusions: The 6-gene signature can help select patients who will benefit from IC and thus lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.
Distinct transcriptional profiles in plasma exosomes associated with recurrence of nasopharyngeal carcinoma patients with standard treatment.
Authors: Li Yongjiang , Zheng Xue , Xie Xiaoqi , Hu Yukai , Kang Jingbo , Wei Jiyu , Wang Ruoyu , Mao Beibei , Qu Baolin , Yang Ying , Li Xianfeng , Fu Xueying , Li Qingyun , Zhang Henghui , Wang Junjie , Wang Feng 
Published: May 2020

6534 Background: Nasopharyngeal carcinoma (NPC) is endemic with a high prevalence in Southern China, Asia,cetuximab and North Africa. Exosomes are small vesicles containing a wide range of functional proteins, mRNA and miRNA. In the progression of NPC, the tumor cells constantly release exosomes into the surrounding environment and also into the circulating blood. The aim of this study was to explore the association between RNA expression in plasma exosomes and prognosis of NPC patients after standard treatment. Methods: In this retrospective study, a total of 25 eligible NPC patients were included: 12 patients in the recurrence (R) subgroup and 13 patients in the no recurrence (NR) subgroup. RNA was extracted from the exosomes of plasma specimens which were collected at West China Hospital, Sichuan University. Gene expression profiles were conducted by using the RNA-sequencing platform. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between R and NR subgroups. The gene set variance analysis (GSVA) was performed to explore C5 gene sets enrichment related to the recurrence after standard treatment. Results: We observed 332 DEGs between R and NR subgroups, which include 125 up-regulated and 207 down-regulated genes (R vs. NR,∣log2fold change∣>1, p<0.05). Moreover, hierarchical clustering analysis of the 332 DEGs revealed that all samples clustered into two subgroups, with cluster 1 containing 82% (9/11) recurrence patients and cluster 2 containing 79% (11/14) no recurrence patients. Further, univariate Cox regression analysis showed that 293 out of 332 DEGs were significantly correlated with DFS ( p<0.05), such as TRAM1, CAPN1, SAT1 and ACTB. GSVA and Log Rank test of survival data demonstrated that a total of 824 pathways/biological processes were significantly different between R andNR subgroups ( p<0.05). Specifically, the top 9 pathways/biological processes, such lipoxygenase pathway, rough endoplasmic reticulum membrane and low density lipoprotein particle clearance, was mainly enriched in the NR subgroup ( p <0.001). Conclusions: Profiling of plasma exosomes RNA in NPC patients reveals distinctive gene expression pattern between patients with or without recurrence. Further functional analysis revealed that top enriched 9 pathways/biological processes may correlate with a favorable prognosis and are worth investigating. Moreover, for the prognosis of patients with NPC, RNA expression of plasma exosomes may be a potentially valuable research object.
Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma (NPC).
Authors: Walsh Robert John , Nickles Emily Pauline , Li Yating , Dharmadhikari Bhushan , Koh Mickey , Ho Liam Pock , Chan Marieta , Koh Liang Piu , Poon Michelle Li Mei , Tan Lip Kun , Huang Yiqing , Ang Yvonne Li'en , Chong Wan Qin , Asokumaran Yugarajah , Loh Kwok Seng , Soo Ross A. , Lim Chwee Ming , Schwarz Herbert , Goh Boon Cher 
Published: May 2020

6535 Background: Epstein-Barr virus (EBV) is associated with non-keratinising (NK) NPC, a disease prevalent in Southeast Asia, and provides a potential target for dendritic cell (DC) vaccine therapy. CD137 ligand (CD137L) expressed on antigen presenting cells costimulates CD137 expressing T cells upon receptor/ligand interaction. CD137L signalling differentiates monocytes to CD137L-DC, a novel type of DC, which are more potent than classical DC in stimulating autologous T cells. Here, we explore the safety and efficacy of autologous CD137L-DC pulsed with EBV peptides spanning Epstein Barr nuclear antigen 1, latent membrane protein 1 (LMP1) and LMP2 (CD137L-DC-EBV-VAX) in patients with locally recurrent or metastatic NPC. Methods: In this single centre, phase I study, eligible patients (pts) with locally recurrent or metastatic NK-NPC and clinical benefit (CB) from their prior treatment (stable disease [SD], partial [PR] or complete response[CR]), underwent apheresis to isolate monocytes which were differentiated to CD137L-DC through CD137L agonist exposure. CD137L-DC were pulsed with EBV antigens during maturation to obtain CD137L-DC-EBV-VAX which was administered intradermally every 2 weeks (w) for up to 7 injections following site preconditioning with Tetanus and Diphtheria vaccine. Results: 14 pts were enrolled of which 2 progressed rapidly and did not begin treatment. Mean age was 58 years. Median lines of prior treatment for metastatic NPC was 1 (range 1-6), the most common being cisplatin and gemcitabine. 9 pts received 7 vaccine doses (range 2-7) with a mean administered cell count of 23.9x106. CB was seen in 5 cases (42%) with 1 PR and 4 SD beyond 1 year. Median progression free survival (mPFS) was 26w (95% CI, 23-43). The lowest PFS (8w) was in a pt with 6 prior lines of treatment including a checkpoint inhibitor. Mean pretreatment neutrophil: lymphocyte ratio (NLR) was 3.4 and a value of less than 3 was associated with prolonged mPFS (42 vs 14w, p = 0.01). Enzyme linked immune absorbent spot (ELISPOT) analysis in 5 pts with CB showed a rise in interferon-γ secreting peripheral T cells prior to the 3rd vaccine versus baseline. Treatment was well tolerated with only 4 cases of grade 1 related adverse events reported, most commonly injection site reaction (3pts). Conclusions: CD137L-DC-EBV-VAX is safe and exhibits promising efficacy when administered following CB from chemotherapy. A rise in activated peripheral blood mononuclear cells after 2 vaccinations in selected patients showing benefit suggests immunological correlates with efficacy. Clinical trial information: NCT03282617 .
Correlation of tumor mutational burden (TMB) with CDKN2A and TP53 mutation in HPV-negative head and neck squamous cell carcinoma (HNSCC).
Authors: Burtness Barbara , Deneka Alexander , Baca Yasmine , Serebriiskii Ilya , Parker Mitchell I. , Nicolas Emmanuelle , Lee Jong Woo , Wise-Draper Trisha , Sukari Ammar , Somer Bradley G. , Golemis Erica 
Published: May 2020

6552 Background: The tumor suppressors TP53 and CDKN2A are commonly mutated or lost in HNSCC, impairing G1 checkpoints. This reduces ability to repair DNA damage arising from hypoxia, replication stress, and mutagen exposure, thus increasing TMB, a potential predictive biomarker for immunotherapy benefit. TP53 mutations can be classified as loss-of-function (LOF) with or without dominant negative (DNE) activity, gain-of-function (GOF) and benign. We investigated whether specific categories of TP53 mutation were associated with increased TMB, and whether these cooperated with CDKN2A mutation to elevate TMB. Methods: We analyzed 1010 HPV- HNSCC tumor samples (246 female) profiled with a 592-gene panel by Caris Life Sciences from 2015 to 2019. Predominant subsites were oral cavity (285), oropharynx (225) and larynx (153). TMB reflected all somatic nonsynonymous missense mutations detected. We report mean TMB per megabase (MB). Pathogenicity of TP53 and CDKN2A mutations was determined according to American College of Medical Genetics (ACMG) guidelines. We also used four alternative methods of characterizing TP53 mutations based on analysis of protein structure, public databases (IARC, ClinVar, InterVar), and publications (PMID: 25108461 and others) assessing structure-function relations. Results: 60% of cases had TP53 mutations ( TP53mut) designated pathogenic by ACMG guidelines. Estimates of frequency of LOF/DNE mutations ranged from 30-42.8% of cases among the alternative classification methods. Damaging CDKN2A mutations were present in 20%. Average TMB per MB varied from 8.2/8.6 (females/males) in oral cavity cancers to 26.5/27.7 (females/males) in cancer of the lip. Mean TMB was typically higher in the presence of damaging LOF/DNE TP53 mutations or CDKN2A mutations, but not TP53 GOF mutations. Based on ACMG, for tumors with TP53 and CDKN2A wild type (WT) TMB was 8.03, for those with CDKN2Amut-only 9.82, for TP53mut-only 10.56, and TP53 mut/CDKN2A mut 17.6 (p < 0.001). For disruptive TP53mut (Poeta algorithm), mean TMB for WT/WT was 8.67, for TP53mut 11.31, CDKN2Amut 17.9 and TP53mut/CDKN2A mut 15.83 (p < 0.001). Conclusions: Mutation of TP53 and/or CDKN2A is associated with increased mean TMB relative to WT; mean TMB was highest for tumors bearing damaging mutations in both genes. GOF TP53 mutation was not clearly associated with increased TMB. As TMB is evaluated as a predictive biomarker in the immunotherapy of HNSCC, specific TP53/CDKN2A mutational status should also be evaluated.
Does sinonasal cancer survival differ based on human papillomavirus status?
Authors: Pusapadi Ramkumar Shreya , Bukatko Aleksandr R , Simpson Matthew C , Adjei Boakye Eric , Ward Gregory M , Antisdel Jastin L , Osazuwa-Peters Nosayaba 
Published: May 2020

6565 Background: The sinonasal tract is a lesser known “hot spot” for the human papillomavirus (HPV), compared with the oropharynx. Additionally, unlike the oropharynx, the role of HPV tumor status in the survival and overall prognosis of the sinonasal tract and other non-oropharyngeal head and neck cancer sites remains inconclusive. Understanding differences in survival based on HPV status could be useful clinically, as it has been for HPV-positive oropharyngeal disease. This study examined whether there are survival differences in sinonasal cancer based on HPV status. Methods: This study included adult sinonasal cancer cases diagnosed between 2010 and 2015 in the National Cancer Database. A multivariable Cox proportional hazards model estimated the association between sinonasal cancer HPV status (HPV-positive, HPV-negative) and all-cause mortality while controlling for covariates (sex, age, race/ethnicity, insurance status, urban/rural, county-level household income, county-level percentage without high school diploma, comorbidity score, stage, histology, facility type, and treatment). A second multivariable proportional hazards model stratified HPV-positive tumor status by high-risk HPV (16, 18, 26, 31, 33, 35, 36, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, and 85) vs. low-risk HPV (6, 11, 32, 34, 40, 42, 44, 54, 61, 62, 64, 71, 72, 74, 81, 83, 84, 87, and 89) and compared their all-cause mortality to HPV-negative patients. Results: There were 1,750 sinonasal cancer patients included in this study, and 484 (27.7%) had HPV-positive disease. Among patients with HPV-positive disease, 75.6% had high-risk types. Mortality risk among all HPV-positive patients combined was 23% lower than HPV-negative patients (aHR = 0.77; 95% CI 0.64, 0.93). After stratifying by high-risk vs. low-risk HPV, high-risk HPV positive patients had 30% lower mortality risk than HPV-negative patients (aHR = 0.70; 95% CI 0.57, 0.88) while risk of mortality did not significantly differ between low-risk HPV-positive patients and HPV-negative sinonasal cancer patients. Conclusions: Sinonasal cancer shows differential survival based on HPV status, and sinonasal cancer patients positive for high-risk HPV had a significantly greater survival advantage than low-risk strains and those with HPV negative disease. HPV status might yet play a role in prognostication of sinonasal cancer, if future studies confirm these findings.
Association of sarcopenia with higher toxicity and poor prognosis in nasopharyngeal carcinoma.
Authors: Hua Xin , Ling Guo , Lin Huan-Xin 
Published: May 2020

6568 Background: Given the growing evidence that sarcopenia is associated with toxicity and survival in various cancers, we investigated its significance in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). Methods: In this retrospective analysis, we studied 862 NPC patients who had received CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography (CT) simulation scans at the third cervical (C3) vertebral level. Receiver-operating characteristic (ROC) curve analyses were used to determine the optimal cutoff values. Propensity score matching (PSM) was applied to develop comparable cohorts of patients with or without sarcopenia. Results: A total of 862 patients were included as the primary cohort, and 308 patients were matched and regarded as the matched cohort. In the primary cohort, the five-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates for the sarcopenia group vs. non-sarcopenia group were 78.2% vs. 93.6% ( P <0.001), 89.4% vs. 87.9% ( P = 0.918), and 82.5% vs. 89.0% ( P = 0.007), respectively. Univariate and multivariate survival analyses revealed that sarcopenia was an independent predictor of OS ( P <0.001 and P <0.001) and DMFS ( P = 0.009, P = 0.034). Patients with sarcopenia experienced significantly higher rates of treatment-related toxicities compared with patients without sarcopenia ( P= 0.032). In addition, patients with sarcopenia also experienced significantly worse treatment response than those without sarcopenia ( P = 0.004). Similar results were found in a PSM cohort. Conclusions: The current findings support that sarcopenia is a promising indicator for predicting clinical outcomes in NPC patients receiving CCRT. A simple and rapid analysis on CT simulation images can provide information about the therapeutic toxicity and survival prognosis, consequently guiding personalized multi-modality interventions during CCRT.