bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of head and neck squamous cell carcinoma response to taxane chemotherapy treatment in the pre versus post nivolumab era.
Authors: moloney carolyn , Sukor Sue , McCarthy Michael Thomas , Grant Cliona 
Published: May 2020

e18504 Background: Nivolumab received FDA approval as monotherapy for the treatment of recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck after failure of platinum-based therapy in 2016. This approval was based on CheckMate 141. When patients ultimately relapse after immunotherapy in the second line setting, third line agents include single agent or combination treatment with a Taxane. Methods: We identified patients with metastatic or recurrent squamous cell head and neck cancer in an Irish hospital who had received Taxane chemotherapy after immunotherapy. We looked at outcomes for these patients including progression free survival (PFS) and overall survival (OS). We then identified a group of patients who received a Taxane following platinum failure in the pre-Nivolumab era to act as a comparator. Our objective was to compare PFS and OS to subsequent Taxane chemotherapy in the era before and after the introduction of Nivolumab as a therapy for platinum refractory head and neck SCC. Results: This retrospective cohort study was made up of 26 patients with metastatic or recurrent head and neck cancer. Primary sites included oropharynx, oral cavity, larynx and nasal cavity squamous cell cancers. The patients had a median age of 56. 13 of these patients identified had progressed on Nivolumab but remained fit for a next line of treatment. Median PFS in this group on Taxane based chemotherapy in the third line setting was 3.8 months. Median OS post progression on Nivolumab was 10 months. One patient remarkably had a complete response to Paclitaxel chemotherapy after progression on previous lines of treatment including immunotherapy, platinum chemotherapy and radiotherapy. We then identified a group of 13 patients with metastatic or recurrent head and neck cancer that had progressed on platinum based therapy in the era before Nivolumab was available. Median PFS after Taxane second line chemotherapy was 2.2 months. Median OS in this group after progressing on platinum treatment was 5.8 months. Conclusions: We set out to share our experience of real-world outcomes for head and neck cancer patients in the Nivolumab era. We found that our patients have shown to have an improved overall survival benefit with subsequent Taxane chemotherapy after immunotherapy compared to those who have not received immunotherapy. All fit patients should be considered for Taxane therapy post failure of Nivolumab.
Indication of adjuvant chemoradiation post neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer.
Authors: Das Sudeep , Patil Vijay Maruti , Noronha Vanita , Dhumal Sachin Babanrao , Joshi Amit , Menon Nandini Sharrel , Srinivas Sujay , Vallathol Dilip Harindran , D'souza Hollis , Prabhash Kumar 
Published: May 2020

e18505 Background: Adjuvant chemoradiation (ACRT) is indicated in the presence of margin positivity or extranodal extension. However, indications of ACRT post neoadjuvant chemotherapy (NACT) is not well defined. At our centre, ACRT is administered in the majority of patients who undergo NACT. This analysis was performed to identify indications for the avoidance of ACRT post NACT. Methods: 160 very locally advanced borderline resectable HNSCC who underwent surgery after NACT were selected. The adjuvant treatment administered was either radiation or chemoradiation at the discretion of the joint clinic. The post-surgical tumour and nodal specimen were graded in accordance with modified tumour regression grade (MTRG). Where grade 1 indicated a complete pathological response. The primary endpoint was disease-free survival (DFS). The patients were divided into 3 biological distinct classes. Group-1 had a pathological complete response (CR) in both tumour and nodes, Group-2 had pathological CR in either tumour or nodes and Group 3 had no pathological CR. Kaplan Meier method was used for the estimation of DFS. The stratified (for groups) log-rank test was used for evaluating the impact of adjuvant radiation. Stratified Cox regression analysis was used for the calculation of hazard ratio. A p-value of 0.05 was considered significant. Results: There were 56 patients (35%) in group 3, 75 (46.9%) in group 2 and 29 (18.1%) in group 1. The overall median DFS was 89.067 months (95%CI 15.345-162.788). The 5-year DFS was 22.1% in group 3, 75.4% in group 2 and 92.3% in group 1 ( P-value < 0.0001). Adjuvant radiation was received by all patients and concurrent chemotherapy was received by 134 (83.8%) patients. Use of concurrent chemotherapy decreased the hazard of disease recurrence (HR-0.297 95%CI 0.135-0.656, P-value = 0.003). The stratified log-rank test p-value was 0.002. Conclusions: Adjuvant chemoradiation is needed after neoadjuvant chemotherapy in very locally advanced borderline resectable head and neck cancer
The impact of locoregional treatment on response to nivolumab in advanced platinum refractory head and neck cancer: The need trial.
Authors: Botticelli Andrea , Mezi Silvia , Pomati Giulia , Sciattella Paolo , Roberto Michela , Cirillo Alessio , Mammone Giulia , Cassano Alessandra , Di Dio Carmela , Cortellini Alessio , Pizzuti Laura , Ronzino Graziana , Salati Massimiliano , Vici Patrizia , Merlano Marco Carlo , Nuti Marianna , Marchetti Paolo 
Published: May 2020

e18508 Background: Immunotherapy is the standard of care in the treatment of platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Previous loco-regional treatment could have an impact on the immune system and response to Nivolumab. The aim of this study is to evaluate the efficacy and safety of Nivolumab in a real world population, identifying the impact of the clinic-pathological characteristics and previous treatment in prediction of early progression. Methods: This is a observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received Nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity, from October 2018 to October 2019. We analyzed treatment outcomes in term of early progression (within 3 months), clinical benefit, progression free survival (PFS) and overall survival (OS). To determine the influence on outcomes, the following variables were investigated: primary tumor sub-site, age, gender, ECOG, previous loco-regional treatment, previous systemic therapy, metastatic site. Results: Data from 61 pts were reviewed: 15 oral cavity, 14 oropharynx, 7 hyphofarynx, 19 larynx, 6 paranasal sinus. Median age was 66 years (29-82), 48 pts were men. Forty-nine pts (80%) had performance status (ECOG) ≥ 1 at baseline evaluation. Eleven pts (18%) had only loco-regional recurrence, while 50 pts (82%) had one or more metastatic site. 32 (52%) and 17 pts (28%) had smoking and alcohol abuse history, respectively. 44 pts (72%) received surgery followed by adjuvant radiant treatment at standard dose (28, 46%) or concomitant definitive radiotherapy (16, 26%) as upfront treatment with curative intent. With a median follow up of 4 months (range 1-11), early progression occurred in 39 pts during Nivolumab treatment (64%), while clinical benefit (stable disease and partial response) was achieved in 22 pts (36%). No G3-G4 toxicities occurred. Early progression to Nivolumab was significantly associated to previous loco-regional treatment both at univariate and multivariate analysis (p=0.003 and p= 0.04, respectively). Conclusions: Nivolumab in R/M HNSCC is effective and safe even though burdened with a high early progression rate. Loco-regional treatment, including wide neck dissection and high dose radiotherapy, may compromise the efficacy of Nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.
Comparison of circulating tumor cells and cell-free DNA in the molecular characterization of patients with head and neck cancer.
Authors: Cabezas-Camarero Santiago , García-Barberán Vanesa , De la Orden-García Virginia , Mediero-Valeros Beatriz , Díaz-Millán Isabel , Saiz-Ladera Cristina , Baliu Piqué Mariona , Gonzalo Irene , López-Cade Igor , Ocana Alberto , Díaz-Rubio Eduardo , Pérez-Segura Pedro 
Published: May 2020

e18521 Background: The role of liquid biopsy in diagnosis and therapy monitoring in patients with head and neck cancer has been much less studied compared to other cancers. Our aim was to evaluate the perfomance in the isolation and recovery for molecular characterization of circulating tumour cells (CTC) of a new immunoafinity-based method and to compare it with the molecular diagnostic yield of plasma cell-free DNA. Methods: Patients with recurrent/metastatic (RM) head and neck cancer (HNC) were enrolled prospectively. Forty mililiters (ml) of plasma were collected at one or several time-points. First blood draw was always collected before starting a new therapeutic intervention or at the time of radiologic progression. For CTC detection and isolation, either anti-EpCAM or both anti-EpCAM + anti-EGFR antibodies were used. Digital PCR and castPCR were used to study KRAS and PI3KCA mutations in non-squamous HNC. A 15-gene customized NGS panel was used to characterized both CTC and cfDNA in patients with squamous HNC. Results: Between February 2016 and October 2018, 14 patients with R/M HNC were included (n = 1 local-only disease, n = 10 local and distant disease, n = 3 distant-only disease). Squamous histology (S): n = 9. Non-squamous (NS): n = 5 (1 naso-ethmoidal intestinal-type adenocarcinoma, 1 parotid gland exadenoma pleomorfic carcinoma, 2 parotid-gland salivary duct carcinomas (SDC), 1 parotid-gland high-grade neuroendocrine carcinoma). Twenty-five CTC determinations were performed. In 5 patients serial CTC determinations were performed. Median CTC was 4 (min-max: 0-49). Median CTC among 11 CTC determinations in S-HNC was 4 (min-max: 0-49). Median CTC was 3 CTC (min-max: 0-26) among the 14 determinations performed in NS-HNC. Digital PCR unveiled mutations in CTC and in cfDNA in 2 of 4 patients tested with NS histology (KRAS, PIK3CA), with one of them being concordant for the specific mutation. NGS unveiled mutations in CTC in 7/9 patients and in cfDNA in 6/9 patients, with only one loci-concordant case between CTC and plasma. Conclusions: IsoFlux detected CTC in the majority of patients with R/M HNC, regardless of the histologic type, and allowed for molecular characterization of CTC using different techniques for mutational analysis. Both NGS and digital PCR allowed for the detection in cell-free DNA of commonly mutated genes in HNC. Liquid biopsy should be more actively studied in this disease in order to better define its role in diagnosis and therapeutic monitoring.
Is there a role of functional endoscopic evaluation of swallowing (FEES) in aiding tracheotomy decannulation post oral cancer surgery?
Authors: Sahni Vibhu Ranjan , Chopra Shamit , Bharthuar Anubha 
Published: May 2020

e18523 Background: A significant proportion of patients with oral cancer require perioperative tracheotomy. The altered oral anatomy post surgery significantly impairs the first and second stages of swallowing, resulting in swallowing dysfunction and potential aspiration. There is no priordata on utilization of FEES or other objective tools to predict successful tracheotomy decannulation in patients with oral cancer. Methods: This constituted a retrospective analysis of 237 patients with oral cancer treated at our institution between Feb 2017 and Dec 2019. Seventy two (30.4%)patients underwent perioperative tracheotomy. Post surgery,after excluding patients who were not considered candidates for early decannulation, 48 (65.7%) underwent FEES with the endpoint of tracheotomy decannulation. The number of FEES procedures required for decannulation was correlated with patient and disease-specific variables utilizing Chi square analysis. Results: The rate of successful decannulation was 100%. The mean number of days from tracheotomy to decannulation was 24.9. Thirty two (66.7%) patients underwent decannulation post the first FEES, notablyupon documentation of no penetration or aspiration to three bolus consistencies. However, 33.3% patients needed swallowing therapy followed by a second (18.8%) or a third (14.6%) FEES before they could be decannulated (late decannulation). No patients required a repeat tracheotomy. A significantly higher proportion of individuals at or younger than median age were decannulated earlier, compared with individuals above median age ( p= 0.01). There was no statistically significant difference between early (T1/2) and advanced (T3/4) primary lesions and timing of decannulation ( p= 0.83). The presence of comorbid diabetes mellitus did not correlate with decannulation timing ( p= 0.81). Conclusions: FEES constitutes a reliable, minimally invasive and cost-effective tool to aid successful decannulation across all stages of oral cancer. It may be indicated especially in older individuals. It helps guide swallowing therapy, and thus potentially augments quality of life by tailoring serial evaluations to aid early decannulation.
An in silico comparative planning study investigating the predicted benefit of dysphagia-optimised volumetric arc therapy (Do-VMAT), relative to standard VMAT (S-VMAT), to reduce radiotherapy-associated dysphagia (RAD) in oropharyngeal cancers (OPC).
Authors: Petkar Imran , Dunlop Alex , McQuaid Dualta , Nutting Christopher 
Published: May 2020

e18540 Background: RAD is a significant treatment-related functional morbidity in OPC and is associated with irradiation of the pharyngeal constrictor muscle (PCM). This study investigated whether a novel PCM-sparing Do-VMAT technique reduced the risk of RAD, compared to S-VMAT. Methods: Twenty OPC patients who previously underwent radiotherapy (RT) to bilateral neck were selected for this retrospective study. For each patient, S-VMAT and Do-VMAT plans were created. In both arms, the mucosal and nodal tumour received 65 Gy while the remaining oropharynx and at-risk nodal levels received 54 Gy; delivered in 30 fractions over 6 weeks. For Do-VMAT, a mandatory mean dose constraint of < 50 Gy to the volume of the combined superior (SPCM) and middle PCM (MPCM) together with an optimal dose constraint of < 20 Gy to the volume of inferior PCM (IPCM), lying outside the high-dose clinical target volume, were additionally defined and optimised to minimise PCM dose. Normal tissue complication probabilities for physician-scored RAD at 6 months (RAD6M) were determined as per the model by Christianen et al in which the 2 variables were mean dose to SPCM and supraglottic larynx (SGL). Statistical analysis was performed using paired t tests. Results: All plans had adequate target volume coverage, and dose to critical organs were within acceptable parameters. Dose to the parotid and submandibular glands were similar between the 2 RT techniques. The mean integral dose was 110.8 Gy-litre (standard deviation 17.1) with S-VMAT and 103.4 Gy-litre (15.4) with Do-VMAT, p < 0.001. With Do-VMAT, the average of the mean dose to PCM, SPCM, MPCM, IPCM, and SGL were 9.3 Gy (1.4), 4.7 Gy (1.7), 7.4 Gy (3.6), 22.7 Gy (4.1), and 2.6 Gy (2.3) respectively lower than S-VMAT (p < 0.001 for all). The mean predicted risk for RAD6M was 31.0 % (4.4) with S-VMAT, and 23.9 % (3.8) with Do-VMAT, p < 0.001. The absolute reduction in estimated toxicity risk with Do-VMAT was > 5 %, the minimally clinically important difference, in every patient. Conclusions: Do-VMAT demonstrated clinically relevant reductions in the predicted risk of RAD, compared to S-VMAT, by reducing dose to the PCM in OPC. The clinical benefits of Do-VMAT is being prospectively evaluated in DARS (CRUK/14/014), a randomised phase III study.
Identifying the distant metastasis genes by next-generation sequencing panel in nasopharyngeal carcinoma.
Authors: Hu Man , Yu Jinming , Zhou Zihan , Li Peifeng , Zhang Xianbin , Zhai Limin , Fan Tingyong , Tian Shiyu , Xu Juan , Yang Xinhua , Xu Jin , Yu Shui , Wang Dongqing , Dong Wei , Cao Xiujuan , Yan Hongjiang , Sun Mingping , Ding Xiuping , Xing Jun , Zhang Peng 
Published: May 2020

e18547 Background: Even though local and regional controls have been substantially improved in nasopharyngeal carcinoma (NPC) in the contemporary era of intensity-modulated radiotherapy with extensive use of combined chemotherapy, the distant metastasis becomes the major cause of treatment failure and cancer-related death. To date, the genes contributed to metastasis of NPC is still unclear. The aim of this study was to identify the genes which lead to distant metastasis. Methods: A total of forty primary nonkeratinizing NPC patients were diagnosed at Shandong Cancer Hospital in this study. The formaldehyde-fixed paraffin embedded (FFPE) taken from primary sites or metastatic lymph nodes were performed next-generation sequencing (NGS) panel (Shanghai OrigiMed Co., Ltd.) to determine variated genes, such as single nucleotide variants (SNV), copy number variants (CNV) and rearrangement. These patients were followed up until Febr. 8, 2020. The genes related to distant metastasis were identified by logistic regression. Moreover, this study compared the frequency of mutated gene between our data and Catalog of Somatic Mutations in Cancer (COSMIC) database by the Chi-square test or Fisher’s exact test. Results: The study included 31 men and 9 women. The median age of the patients at diagnosis was 47 years (range 15–71 years). With the median follow-up of 10.6 months (range 16.8–72.3 months), 7 patients had distant metastasis and 1 undergone recurrent. Notably, EMSY and MCL1 variants were contributed to NPC distant metastasis (OR = 31, P = 0.049). The top eight SNV of genes in our study were CYLD, KMT2D, BAP1, EP300, TP53, ATM, NFKBIA and SPEN. When compared to COSMIC database, the mutant frequencies of CYLD, EP300 and BAP1 in our study were significantly higher than that of COSMIC database. However, the mutant frequencies of IDH2 and KMT2C were significantly lower than COSMIC database. Conclusions: This is the first study which suggests that EMSY and MCL1 variants were involved in the metastasis of NPC. The study identified 5 genes, which mutation frequency is significantly different from the COSMIC database. The study provided a molecular basis for a comprehensive understanding of, and exploring targeted therapies for nasopharyngeal carcinoma.
Comparison of intraoperative imprint cytology with frozen section for lymph node metastasis in patients with head and neck cancer.
Authors: Neduvanchery Saheer 
Published: May 2020

e18548 Background: Intraoperative evaluation of lymph nodal metastasis in head and neck carcinoma assumes importance in deciding the extent of lymph node dissection. Frozen section is the most commonly employed technique. But it requires significant investment in terms of resources, time and personnel. Intraoperative imprint cytology is a rapid, reliable and an inexpensive alternative. So we conducted a prospective diagnostic test accuracy study to assess the diagnostic accuracy of intraoperative imprint cytology and frozen section for lymph node metastasis in Head and neck Cancer when compared to Gold standard, which is the final Histopathology. Methods: All patients presenting with squamous cell carcinoma of head and neck with clinically N0 neck undergoing surgery as primary treatment were included in the study. For patients undergoing surgery, neck nodal tissue were sent for intraoperative assessment of clinically suspicious nodes. Intraoperative assessment was done by imprint cytology and frozen section and was reviewed and reported by two independent pathologist. The sensitivity, specificity and accuracy of imprint cytology and frozen section were calculated with reference to the final histopathology report. Time duration for reporting were also calcuted for both. Results: Total 34 patients with clinically N0 neck were included in the study and 85 slides were examined for frozen section and imprint cytology. Occult nodal metastasis was found in 16 patients (47.06%). The mean time duration for reporting for frozen was 41.18 ±3.62 minutes where as for imprint cytology it was 18.12 ±2.01 minutes. The concordance rate between the frozen section and imprint cytology was 94.12%. The sensitivity of frozen section was 100 % where as for imprint cytology it was 85.7 %( p = 0.00). The specificity was 98.6 % for frozen section and 95.8 % for imprint cytology (p = 0. 27). The positive predictive value was 93.3 % and 80 % for frozen section and imprint cytology respectively (p = 0.01). The negative predictive value was 100% for frozen section and 97.1% for imprint cytology (p = 0.12). The accuracy for frozen section was 98.8 % where as for imprint cytology it was 94.1%(p = 0.09). Conclusions: Imprint cytology provides a cheaper, accurate, reliable and a rapid alternative for frozen section for intraoperative assessment of neck nodes in squamous cell carcinoma of head and neck and it assumes importance in resource driven countries like India.
Correlation of pathologic tumor grade with survival in oral cavity squamous cell carcinoma.
Authors: Anderson Eric , Luu Michael , Lu Diana J. , Nguyen Anthony Tuan , Mallen-St. Clair Jon , Scher Kevin , Mita Alain C. , Ho Allen S. , Zumsteg Zachary Stephan 
Published: May 2020

e18557 Background: Pathologic tumor grade is a well-established prognostic risk factor that impacts staging and standard-of-care treatment decisions across multiple cancer types. However, the significance of tumor grade in cancers of the head and neck is less certain. Even in oral cavity squamous cell carcinoma (OCSCC), the head and neck cancer subsite with largest body of literature regarding the predictive value of tumor grade is, the prognostic significance of tumor grade remains controversial. Thus, we sought to better elucidate the prognostic importance of tumor grade in OCSCC. Methods: Patients with OCSCC diagnosed from 2004-2015 and undergoing primary surgery with or without adjuvant treatment in the National Cancer Data Base (NCDB) were identified. Overall survival (OS) was estimated using the Kaplan-Meier method with and without propensity score matching (PSM). Univariate and multivariable survival analyses were performed using Cox regression. Analyses were adjusted for multiple clinicopathologic factors, including age, sex, comorbidity status, year of diagnosis, pathologic staging, margin status, number of lymph nodes (LN) examined/positive, extranodal extension (ENE), lymphovascular invasion (LVI), adjuvant radiation, and concomitant chemotherapy. Results: Median follow-up was 40.7 months. Of 13,941 patients with OCSCC, 2,883 had low-grade tumors, 8,716 had intermediate-grade tumors, and 2,342 had high-grade tumors. Higher tumor grade was strongly associated with decreased survival. Specifically, five year OS was 62.7%, 52.8%, and 42.5% in low-grade (LG), intermediate-grade (IG), and high-grade (HG) OCSCC, respectively (p-value < 0.001). In PSM cohorts, OCSCC patients with high-grade had significantly worse 5 year OS (47.7% vs. 57.7%, p < 0.001) in comparison to those with LG OCSCC. Similarly, patients with IG tumors has worse 5-year OS (55.6% vs. 60.3%, p = 0.001) than patients with LG tumors in PSM cohorts. In multivariable analysis, both HG (HR 1.38, 95% CI 1.25-1.52, p < 0.001) and IG (HR 1.17, 95% CI 1.08-1.26, p < 0.001) OCSCC was associated with worse survival than what was observed in LG tumors. The magnitude of the independent effect of tumor grade in multivariable analysis was greater than or equal to what was observed with other well-established prognostic factors like margin positivity (HR 1.34), ENE (HR 1.35), and LVI (HR 1.18). Conclusions: Pathologic tumor grade is a strong predictor of survival among patients with OCSCC. Tumor grade should be considered when making therapeutic recommendations for OCSCC.