Jack A. Harris, William P. Hunter, Glenn J. Hanna, Nathaniel S. Treister, Reshma S. Menon
Publicatie 24-10-2020
No studies have attempted to examine the role of geographic location on oral squamous cell carcinoma (OSCC) disease progression in the United States (US). The purpose of this study is to analyze rural-urban differences in prognosis and long-term survival in patients with OSCC. This retrospective cohort study utilizes the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) database to examine primary OSCC diagnoses from 1990 to 2015 in the US. The primary predictor variable was patient Rural-Urban Continuum Code (RUCC) (rural vs. urban). The primary outcome variable consisted of overall survival time after initial diagnosis. Additional variables assessed include patient demographics, primary anatomical site of the cancer, histological diagnosis, stage/grade at time of diagnosis, and disease outcome. Descriptive statistics were calculated, and categorical variables were compared. Additional cumulative survival and univariate/multivariate analyses were performed. 46,678 cases of OSCC between 1990 and 2015 were identified. The rural subgroup was more likely to present at the time of diagnosis with a lower grade (p < 0.001) and an earlier stage (p < 0.001). Rural populations demonstrated superior overall survival (p < 0.001), whereas urban populations were more likely to die as a result of their OSCC (p < 0.001). After adjusting for all patient-specific factors, urban status still yielded a poorer disease prognosis. Living in rural areas is associated with better prognosis and long-term survival in patients with OSCC. Further studies are needed to better elucidate the mechanisms underlying these findings.
Pubmed PDF WebSze Min Lek, Ke Li, Qiu Xuan Tan, Nicholas B. Shannon, Wai Har Ng, Josephine Hendrikson, Joey W.S. Tan, Hui Jun Lim, Yudong Chen, Kelvin K.N. Koh, Thakshayeni Skanthakumar, Xue Lin Kwang, Fui Teen Chong, Hui Sun Leong, Gerald Tay, Natascha Ekawati Putri, Tony Kiat Hon Lim, Jacqueline S.G. Hwang, Mei Kim Ang, Daniel S.W. Tan
Publicatie 23-10-2020
We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC. Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3. Validation was performed using immunohistochemistry (IHC) on tissue microarrays (TMAs) of head and neck cancers (n = 333), staining for ATP13A3 and phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA was used to knockdown ATP13A3 expression in patient derived HNSCC cell lines. Protein expression of ATP13A3 and Aurora kinase A was then assessed by immunoblotting. GSEA identified Aurora kinase pathway to be associated with high expression of ATP13A3 (p = 0.026). The Aurora kinase pathway was also associated with a trend towards poor prognosis and tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, the immunohistochemical staining results revealed a significant association between Aurora kinase activity and high ATP13A3 expression (p < 0.001). Knockdown of ATP13A3 in human head and neck cell lines showed decrease in Aurora kinase A levels. Tumors with high ATP13A3 are associated with high Aurora kinase activity. This suggests a potential therapeutic role of Aurora kinase inhibitors in a subset of poor prognosis HNSCC patients with overexpression of ATP13A3.
Pubmed PDF WebKatrine Schneider, Kathrine K. Jakobsen, Jakob S. Jensen, Irene Wessel, Anders Christensen, Lena Specht, Giedrius Lelkaitis, Christian Mirian, Christian v. Buchwald, Christian Grønhøj
Publicatie 18-10-2020
Human papillomavirus infection and p16-overexpression is a principal cause and favorable prognostic factor for oropharyngeal squamous cell carcinomas but the value as prognostic marker in oral cavity squamous cell carcinomas (OSCC) is undetermined. All patients diagnosed with OSCC in Eastern Denmark in the period 2008-2014 were enrolled. Survival estimates were evaluated as overall survival (OS) and progression free survival (PFS) by Kaplan-Meier survival curves and multivariate Cox-regression analyses. We included 575 patients from which 13% (n = 69) had p16-positive tumors. The 5-year OS were 55% and 62% for the p16-negative and p16-positive patients, respectively, and the 5-year PFS were 48% and 50%. In a multivariate survival analysis, p16-positivity showed no significant influence on OS (HR: 1.06 [0.67-1.70], p = 0.79) and PFS (HR: 1.11 [0.76-1.63], p = 0.58). In this population-based cohort of non-selected OSCC patients, we found no difference in survival outcomes when stratified on p16-overexpression status.
Pubmed PDF WebJong Chul Park, Julia Durbeck, John R. Clark, Daniel L. Faden
Publicatie 17-10-2020
To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed. A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen. Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy.
Pubmed PDF WebJames Daniell, Cristian Udovicich, David Rowe, Lachlan McDowell, Domenic Vital, Mathias Bressel, Matthew J.R. Magarey, Tim A. Iseli, Tim Wong, Ernest Lekgabe, Karda Cavanagh, Tsien Fua, Danny Rischin, David Wiesenfeld
Publicatie 11-10-2020
To assess the effect of the histological margins (HM) upon locoregional failure (LRF) and overall survival (OS) for oral tongue squamous cell carcinoma (OTSCC). We undertook a retrospective review of 258 patients, across two institutions, treated for OTSCC between 2007 and 2016. A Cox-proportional hazards model was used to compare the relative hazard ratio of HM to the accepted standard of 5 mm margins for LRF and OS. The median follow up period was 4.8 years. The 5 year OS and freedom from LRF were 69% and 75% respectively. The Cox-proportional hazards model adjusted for age, DOI and LVI showed increasing risk of mortality and LRF with decreasing HM widths of <5 mm. HM >5 mm were associated with a risk reduction of both LRF and mortality in OTSCC. This study supports >5 mm HM being the oncologic goal of surgery.
Pubmed PDF WebKevin J. Contrera, Timothy D. Smile, Chengetai Mahomva, Wei Wei, David J. Adelstein, James R. Broughman, Brian B Burkey, Jessica L. Geiger, Nikhil P. Joshi, Jamie A. Ku, Eric D. Lamarre, Robert R. Lorenz, Brandon L. Prendes, Joseph Scharpf, Larisa M. Schwartzman, Neil M. Woody, David Xiong, Shlomo A. Koyfman
Publicatie 11-10-2020
The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging. Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk. Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and <19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P < .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003). In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design.
Pubmed PDF WebJulius de Vries, Linda Bras, Grigory Sidorenkov, Suzanne Festen, Roel J.H.M. Steenbakkers, Johannes A. Langendijk, Max J.H. Witjes, Bernard F.A.M. van der Laan, Geertruida H. de Bock, Gyorgy B. Halmos
Publicatie 13-10-2020
To determine the effect of frailty on Health Related Quality of Life (HRQoL) after treatment for Head and Neck Cancer (HNC). Patients were prospectively included in OncoLifeS, a data-biobank. Before treatment, patients underwent geriatric screening, including the Groningen Frailty Indicator (GFI) and Geriatric 8 (G8). Patients' HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at three, six, twelve and twenty four months after treatment. Linear mixed models were used for statistical analysis. All models were adjusted for baseline HRQoL values, relevant confounders at baseline and yielded estimates (β), 95% confidence intervals and p-values. 288 patients were included. The mean age was 68.4 years and 68.8% were male. During follow-up, 84 patients had tumor recurrence and 66 died. Response to EORTC-QLQ-C30 ranged from 77.3% to 87.8%. Frail patients, defined by GFI, had significantly worse Global Health Status/Quality of Life (GHS/QoL) (β = -8.70(-13.54;-3.86), p < 0.001), physical functioning (β = -4.55(-8.70;-0.40), p < 0.032), emotional functioning (β = -20.06(-25.65;-15.86), p < 0.001), and social functioning (β = -8.44(-13.91;-2.98), p < 0.003) three months after treatment compared to non-frail patients. Furthermore, frail patients had a significantly worse course of GHS/QoL (β = -7.47(-11.23;-3.70), p = 0.001), physical functioning (β = -3.28(-6.26;-0.31), p = 0.031) and role functioning (β = -7.27(-12.26;-2.28), p = 0.005) over time, compared to non-frail patients. When frailty was determined by G8, frailty was significantly associated with worse GHS/QoL (β = -6.68(-11.00;-2.37), p = 0.003) and emotional functioning (β = -5.08(-9.43;-0.73), p = 0.022) three months after treatment. Frail patients are at increased risk for decline in HRQoL, and further deterioration during follow-up after treatment for HNC.
Pubmed PDF WebShuang Huang, Yongfeng Piao, Caineng Cao, Jia Chen, Wei Sheng, Zekai Shu, Yonghong Hua, Feng Jiang, Qiaoying Hu, Xiaozhong Chen, Yuanyuan Chen
Publicatie 09-10-2020
We investigated the effect of prophylactic oral nutrition supplements (ONS) in locally advanced nasopharyngeal carcinoma patients receiving neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT). Eligible patients were randomly assigned to an intervention or control group. Patients in the intervention group were supported with prophylactic ONS from the beginning of CCRT. The control group received nutritional support only when necessary. Bodyweight, hematological indexes, nutritional status, and quality of life were measured at baseline and before, during, and after RT. We evaluated 114 patients from October 2016 to May 2018. More than half of patients experienced significant weight loss during CCRT, which continued for three months after radiotherapy (RT). Compared to baseline, the rate of weight loss ≥ 5% before, during, at the end of RT, and one and three months after RT were 3.5%, 28.9%, 51.8%, 61.4%, and 61.4%, respectively. Nutritional status and global health status scores progressively decreased during treatment. The rate of RT interruption was higher in the control group than in the intervention group (7.14% vs. 0%, χ Malnutrition and weight loss progressively increased during treatment. Prophylactic ONS can improve tolerance to CCRT, but it offers no advantage on short-term weight loss or nutritional assessment scores.
Pubmed PDF WebHadeel Jawad, Sarah Shahida Ashaari, Ross OShea, Deirdre Callanan, Patrick Sheahan, Linda Feeley
Publicatie 05-10-2020
Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination. Retrospective study of 297 patients with OCSCC who underwent surgery at our institution. Clinical and pathological data were previously populated from review of medical charts and histological reports. Slides were re-reviewed for depth of invasion measurements. Patients were staged using both TNM7 and TNM8 with overall survival statistics analysed. Overall 118 patients (39.7%) were upstaged using TNM8. Both TNM7 and TNM8 stage categories were highly significant for OS (all p values < 0.0001). Hazard discrimination analysis showed that TNM7 could only differentiate stage III from stage IV disease with significance (OS p = 0.01). In comparison TNM8 could distinguish between stage II and III disease (OS p = 0.047) and between stage III and IV disease (OS p = 0.004). Subsite analysis suggested that both editions of the staging system perform best for tongue primaries. Although TNM8 showed improved hazard discrimination in comparison to TNM7, problems with discriminative ability persisted with 8th edition staging criteria. Large scale validation studies will be required to direct future refinement of the staging rules and to establish if the continued use of a single staging system for all oral cavity subsites is appropriate.
Pubmed PDF WebJames C.H. Chow, Anthony H.P. Tam, Ka-Man Cheung, Victor H.F. Lee, Chi-Leung Chiang, Macy Tong, Edwin C.Y. Wong, Alice K.W. Cheung, Sunny P.C. Chan, Jessica W.Y. Lai, Roger K.C. Ngan, Wai-Tong Ng, Anne W.M. Lee, Kwok-Hung Au
Publicatie 28-09-2020
Long-term risk of second primary cancer (SPC) after definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) remains unclear. This study aims to evaluate the risk, predictive factors and survival impact of SPC in a large territory-wide cohort of NPC survivors in an endemic region. In this multicenter study, consecutive NPC patients (n = 3166) who underwent definitive IMRT in all six public oncology centers in Hong Kong between 2001 and 2010 were included. SPC risks were quantified by standardized incidence ratios (SIRs) and absolute excess risks (AERs) estimated from corresponding age-, sex-, and calendar year-specific population cancer incidence data from the Hong Kong Cancer Registry. Predictive factors and SPC-specific mortality were analyzed. Over a median follow-up period of 10.8 years, 290 cases of SPC were observed with a crude incidence of 9.2%. Cancer risk in NPC survivors was 90% higher than that in general population [SIR, 1.9; 95% confidence interval (CI), 1.7-2.2], with an AER of 52.1 (95% CI, 36.8-67.3) per 10,000 person-years at risk. Significant excess cancer risks were observed for oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung. Advanced age, smoking, hepatitis B status, and re-irradiation were independent predictive factors. SPC accounted for 9.4% of all deaths among NPC survivors during the study period, and 10-year SPC-specific mortality was 3.4%. Second cancer risk after IMRT was substantial among NPC patients. SPC impairs long-term survival, and close surveillance is warranted as part of survivorship care.
Pubmed PDF WebSteffen Spoerl, Michael Gerken, René Fischer, Andreas Mamilos, Silvia Spoerl, Stefanie Wolf, Fabian Pohl, Christoph Klingelhöffer, Tobias Ettl, Torsten E. Reichert, Gerrit Spanier
Publicatie 09-10-2020
Numerous studies analyzed lymphovascular invasion (LVI) in various malignant diseases, however, little is known about the role of lymphatic invasion (LI) as well as vascular invasion (VI) in oral squamous cell carcinoma (OSCC). The aim of this study is to illuminate the role of LI and VI in a population-based cohort study. We retrospectively analyzed 745 primarily resected OSCC patients in Eastern Bavaria for histopathologically verified LI and VI. Overall survival (OS) and recurrence-free survival (RFS) were calculated, whereas analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.4 years. LI was found in 115 patients (15.4%), VI was diagnosed in 23 cases (3.1%). LI correlated significantly with distinct anatomical sites (p = 0.004), increasing pT-classification (p < 0.001), lymph node involvement (p < 0.001), higher grading (p < 0.001), advanced UICC-stages (p < 0.001) and adjuvant therapies (p < 0.001). Similar results were found for VI. Survival analysis resulted in a significantly decreased five-year OS and RFS in patients with diagnosed LI (OS: 41.1%, RFS: 38.3%) in contrast to LI-negative cases (OS: 66.8%, RFS: 59.7.7%, p < 0.001). Analogous outcomes were seen for patients with VI. Additionally, LI was identified as a predictive parameter, indicating individual patients' response to adjuvant therapies. This population-based cohort study underlines the unfavorable aspect of LI and VI on outcome in OSCC. Including LI and VI in existing staging systems could help to stratify patients' risk for adverse outcome and consecutively determine adjuvant treatment in malignant disease.
Pubmed PDF WebPanagiota Economopoulou, Ioannis Kotsantis, George Papaxoinis, Niki Gavrielatou, Maria Anastasiou, Anastasios Pantazopoulos, George Kavourakis, Stavros Gkolfinopoulos, Ioannis Panayiotides, Alexandros Delides, Amanda Psyrri
Publicatie 26-09-2020
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this retrospective study was to investigate the association between irAEs and disease outcome in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study included 89 patients with R/M HNSCC who were treated with nivolumab in our center from October 2015 to January 2020. Overall survival (OS) and post-progression survival (PPS) were calculated from the date of nivolumab initiation or from the date of progression on nivolumab respectively to the date of death or censored at the last date of follow up. Twenty-four patients (27%) developed irAEs, with more common thyroiditis (N = 13, 14.6%). ORR did not differ between patients with irAEs (29.2%) and patients without irAEs (21.9%, p = 0.576). Median PFS was similar between the two groups (3.1 months for patients with irAEs vs. 2.6 months for patients without irAEs, p = 0.412). Median OS was significantly longer in patients with irAEs (17.9 vs. 6.3 months in patients without irAEs, log-rank p = 0.004). Additionally, median PPS was significantly improved in patients who developed irAEs (10.2 months vs. 2.8 months for patients without irAEs, log-rank p = 0.001). In multivariate analysis, the development of irAEs and response to nivolumab were shown to be independent prognostic factors for favorable OS and PPS. The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with nivolumab.
Pubmed PDF WebArdalan Ebrahimi, Ruta Gupta, Peter Luk, Tsu-Hui (Hubert) Low, Lachlan McDowell, Matthew J.R. Magarey, Paul N. Smith, Diana M. Perriman, Klaus-Martin Schulte, Michael Veness, Sandro V. Porceddu, Jonathan R. Clark
Publicatie 25-08-2020
We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification. Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ± adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE. The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage. Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.
Pubmed PDF WebRamez Philips, Michael C. Topf, Meghan B. Crawley, Brian Swendseid, Adam Luginbuhl, Joseph Curry, David Cognetti
Publicatie 23-08-2020
To determine if elderly patients (≥70 years) have differences in functional and survival outcomes compared to non-elderly patients (<70 years) following transoral robotic surgery. A retrospective cohort study was conducted on patients undergoing robotic surgery for head and neck cancer at a tertiary institution from 2011 to 2016. Functional status was evaluated with diet, enteric feeding status, Functional Oral Intake Scale (FOIS), tracheostomy tube placement, and unplanned readmission. Kaplan Meier method and Cox proportional hazard model were used to assess overall survival (OS) and disease-free survival (DFS) between elderly and non-elderly patients. Two hundred and forty-six patients met inclusion criteria. The mean age of the cohort was 63.5 ± 9.74 years. There were 64 patients (26.0%) that were ≥70 years. Elderly patients were more likely to be discharged with enteric access (p < 0.002). As early as 3 months, there was no significant difference in need for enteric feeds, diet, or FOIS score. There was no difference in tracheostomy tube rates and unplanned readmission between both cohorts. There was no significant difference in OS and DFS between age groups when stratified by p16 status. Elderly patients are more likely to require perioperative enteric feeding, but 3-month, 1-year, and 2-year functional outcomes are comparable to younger patients. Survival outcomes are similar in both populations.
Pubmed PDF WebAbhishek Mahajan, Ankita Ahuja, Nilesh Sable, Hilda E. Stambuk
Publicatie 21-08-2020
Laila A. Gharzai, Pin Li, Matthew J. Schipper, John Yao, Charles S. Mayo, Joel R. Wilkie, Peter G. Hawkins, Teresa Lyden, Anna Blakely, Mohannad Ibrahim, Caitlin A. Schonewolf, Jennifer Shah, Avraham Eisbruch, Keith Casper, Michelle Mierzwa
Publicatie 18-08-2020
Improved prognosis for p16+ oropharyngeal squamous cell carcinoma (OPSCC) has led to efforts to mitigate long-term complications of treatment, which remains poorly defined in late survivors. Here we characterize very late dysphagia in OPSCC. Long-term review of 93 p16+ OPSCC patients treated with chemoradiation was performed. We scored videofluoroscopic swallow studies (VFSS) according to the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Very late dysphagia was defined >2.5 years from end of treatment. Fine-Gray regression models were used to assess dysphagia with competing risk of death. Median follow up was 10.5 years. 402 total VFSS were assessed (median 4 per patient, range 0-8). 15.1% of patients had a DIGEST score ≥2 very late after treatment. Very late DIGEST score ≥2 correlated with T-stage (HR 1.7, p = 0.049), second cancer (HR 6.5, p = 0.004), superior pharyngeal constrictor dose (HR 1.11, p = 0.050), total tongue dose (HR 1.07, p = 0.045), but not hypoglossal nerve dose (p > 0.2). Seven patients (7.5%) had late progressive dysphagia, defined as DIGEST score that increased by ≥2 beyond one year after treatment, and this correlated with higher ipsilateral hypoglossal nerve D1cc dose (75 vs 72 Gy, p = 0.037). In p16+ OPSCC patients treated with definitive chemoradiation, at least 7.5% developed late progressive dysphagia, and 15.1% experienced moderate dysphagia >2.5 years from treatment. Our study suggests that dose to tongue musculature may be associated with very late dysphagia, and hypoglossal nerve dose may be associated with late progressive dysphagia. More intensive long-term dysphagia survivorship monitoring is suggested.
Pubmed PDF WebMeng Sun, Yuan Qu, Kai Wang, Runye Wu, Ye Zhang, Shiping Zhang, Jianping Xiao, Junlin Yi, Li Gao, Guozhen Xu, Xiaodong Huang, Jingwei Luo
Publicatie 17-08-2020
This study is aimed to evaluate the long-term outcomes and management approaches in different histological subtypes of primary nasopharyngeal adenocarcinoma (NPAC). 71 patients with NPAC at our institution between 1984 and 2016 were reviewed, including adenoid cystic carcinoma (ACC) in 43 patients, mucoepidermoid carcinoma (MEC) in 17 patients, and primary traditional adenocarcinoma (AC) in 11 patients. 37 patients received primary radiotherapy and 34 patients underwent primary surgery. The median time of follow-up was 77 months. The 5-year overall survival rate (OS), locoregional failure-free survival rate (LRFFS) and distant metastasis failure-free survival rate (DFFS) were 69.9%, 67.1% and 77.9%, respectively. Patients who received combined modality therapy had better 5-year OS (73.7% vs 66.2%, p = 0.065) and LRFFS (73.1% vs 64.5%, p = 0.047) than patients receiving single modality therapy. Regarding the different histological subtypes, the survival rates of patients with ACC undergoing primary radiotherapy and primary surgery were similar (5-year OS 82.3% vs 68.8%, LRFFS 70.0% vs 70.8%, p＞0.05). As to patients with MEC and AC, those who underwent primary surgery achieved better 5-year OS (75.6% vs 45.5%, p = 0.001) and LRFFS (70.6%% vs 57.1%, p = 0.014) than those who received primary radiotherapy. Multivariate analyses indicated that histological subtypes and radiotherapy technique were independent factors for OS. The optimal treatment policy for NPAC remained the combination of radiotherapy and surgery. For patients with ACC, radiotherapy could be considered as the primary treatment. Surgery was suggested to be the primary treatment in patients with MEC and AC.
Pubmed PDF WebChristina A. Wicker, Vinita Takiar, Rangaswamy Suganya, Susanne M. Arnold, Yolanda M. Brill, Li Chen, Craig M. Horbinski, Dana Napier, Joseph Valentino, Mahesh R. Kudrimoti, Guoqiang Yu, Tadahide Izumi
Publicatie 18-08-2020
Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p = 0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p < 0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p = 0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p < 0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p < 0.05). The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.
Pubmed PDF WebJung Hwa Moon, Sang Hyuk Lee, Bon Seok Koo, Jin Man Kim, Songmei Huang, Jae Hoon Cho, Young Gyu Eun, Hyang Ae Shin, Young Chang Lim
Publicatie 11-08-2020
The acquisition of stem-like phenotype is partly attributed to the induction of epithelial-mesenchymal transition (EMT). Thus, the activation of factors involved in EMT can be linked to cancer stem cell genesis. However, the underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. Herein, we investigate whether slug, one of the major effectors of EMT, affects the stemness of HNSCC cells. We performed in vitro experiments to determine whether slug gene manipulation can influence the stemness phenotypes, including the capacity for self-renewal, expression of putative stemness markers, chemoresistance, and invasion in HNSCC cells. Further, we identified whether Slug knockout attenuates tumorigenicity of HNSCC cells in vivo. Finally, we examined whether prognosis of HNSCC patients after curative treatment may be affected by the level of slug expression. Overexpression of slug promoted self-renewal of HNSCC cells via activation of sphere formation, the expression of stem cell markers, and induction of chemoresistance to cisplatin. Also, slug overexpression increased the migration and invasion of HNSCC cells in vitro and was mainly observed during the invasion in HNSCC xenograft mouse model. By contrast, slug expression knockdown abrogated their self-renewal capacity, stemness-associated gene expression, and cisplatin chemoresistance. Furthermore, high levels of slug expression correlated with poor prognosis of patients with HNSCC. Inhibition of slug expression may represent a novel therapeutic strategy targeting HNSCC stem-like cells.
Pubmed PDF WebCornelia G.F. van Lanschot, Yoram P. Klazen, Maria A.J. de Ridder, Hetty Mast, Ivo ten Hove, José A. Hardillo, Dominiek A. Monserez, Aniel Sewnaik, Cees A. Meeuwis, Stijn Keereweer, Yassine Aaboubout, Elisa M. Barroso, Quincy M. van der Toom, Tom C. Bakker Schut, Eppo B. Wolvius, Robert J. Baatenburg de Jong, Gerwin J. Puppels, Senada Koljenović
Publicatie 10-08-2020
Depth of invasion (DOI) is the most important predictor for lymph node metastasis (LNM) in early stage (T1-T2) oral cancer. The aim of this study is to validate the cut-off value of 4 mm on which the decision to perform an Elective Neck Dissection (END) is made. We performed a retrospective study in patients with pathologically proven early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiological signs of LNM, who were treated between 2013 and 2018. An END was performed when DOI was ≥ 4 mm and a watchful waiting protocol was applied in patients with DOI < 4 mm. Three hundred patients were included. END was performed in 77% of patients with DOI ≥ 4 mm, of which 36% had occult LNM (pN+). Patients in the watchful waiting group (48%) developed a regional recurrence in 5.2% for DOI < 4 mm and 24.1% for DOI ≥ 4 mm. For DOI ≥ 4 mm, regional recurrence free survival was higher for patients who were treated with END compared to watchful waiting (p = 0.002). A Receiver-Operator-Curve -analysis showed that a DOI cut-off value of 4.0 mm was the optimal threshold for the prediction of occult LNM (95.1% sensitivity, 52.9% specificity). A DOI of ≥ 4 mm is an accurate cut-off value for performing an END in early stage OCSCC. END results in higher survival rates and lower regional recurrence rates in patients with DOI ≥ 4 mm.
Pubmed PDF WebWenlu Li, Qiuyu Zhu, Sanke Zhang, Lei Liu, Han Zhang, Dandan Zhu
Publicatie 09-08-2020
Oral squamous cell carcinoma (OSCC) is an aggressive cancer type in head and neck. A number of long non-coding RNAs (lncRNAs) are discovered to serve regulatory roles in OSCC. HOXC13 antisense RNA (HOXC13-AS) has been proved to behave as a tumor-facilitator in nasopharyngeal carcinoma, but its regulatory role in OSCC has never been investigated. In this study, GEPIA indicated that HOXC13-AS and its neighbor gene HOXC13 were upregulated in HNSC samples, and we consistently unveiled their upregulation in OSCC tissues and cell lines. Silencing HOXC13-AS abrogated OSCC cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT). Moreover, HOXC13 overexpression rescued the influences of HOXC13-AS silence on OSCC cellular processes and in vivo tumor growth. Mechanistically, HOXC13-AS upregulated HOXC13 expression in OSCC through sequestering miR-378g, which was proved to exert suppressive functions in the malignant behaviors of OSCC cells. Further, HOXC13 was revealed to be positively correlated with HOXC13-AS and negatively with miR-378g in expression in OSCC samples. In sum, our findings suggested that HOXC13-AS functioned as a ceRNA to accelerate the malignant behaviors of OSCC cells via miR-378g/HOXC13 axis, shedding a new light on the lncRNA-targeted treatment for OSCC.
Pubmed PDF WebTseng-Cheng Chen, Chen-Tu Wu, Cheng-Ping Wang, Pei-Jen Lou, Jenq-Yuh Ko, Yih-Leong Chang
Publicatie 10-08-2020
To determine the tumor genomic, immunologic expression, and risk factors of treatment outcomes for patients with double head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC). We reviewed patients with double HNSCC and ESCC between 1995 and 2014. The TP53 genomic mutation, CD8+ tumor infiltrating lymphocytes (TIL) and tumor programmed cell death ligand 1 (PD-L1) expression of paired HNSCC and ESCC were analyzed. A total of 116 patients (57 metachronous and 59 synchronous) were included. There were 88 (75.86%) patients with HNSCC and 80 (68.97%) with ESCC harboured TP53 disruptive mutation. Nearly 106 (91.38%) patients had different clonality of TP53 mutation in paired HNSCC and ESCC. The immunologic expression of synchronous and metachronous patients was significantly different. Compared to the metachronous patients, the synchronous patients had significantly higher HNSCC CD8+ TIL (p = 0.03), ESCC CD8+ TIL (p < 0.001), HNSCC PD-L1+ tumor proportion score (TPS, p = 0.04), and ESCC PD-L1+ TPS (p = 0.04). Furthermore, among the synchronous patients, the immunologic expression between HNSCC and ESCC was significantly correlated. The CD8+ TIL and PD-L1 TPS had strongly (r = 0.63, p < 0.0001) and moderately (r = 0.42, p = 0.001) positive correlations, respectively. Finally, advanced stage (III/IV) HNSCC was a significant factor for disease-free (p = 0.03) and overall survival (p = 0.005). In patients with double HNSCC and ESCC, nearly all HNSCC and ESCC were of multicentric origin. For the synchronous patients, there was more adaptive immune resistance in HNSCC and ESCC. The immunologic expression between paired HNSCC and ESCC was also significantly correlated.
Pubmed PDF WebJun Wang, Chen-Lu Lian, Hua Zheng, Li-E Lin, Yi-Feng Yu, Qin Lin, San-Gang Wu
Publicatie 09-08-2020
This prospective study aimed to assess the incidence, details of the change of cognitive dysfunction, and predictive factors of cognitive function impairment associated with induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients. We prospectively included NPC patients who treated with IC from December 2018 to January 2020. Montreal cognitive assessment (MoCA) was used to measure cognitive function, and score less than 26 was defined as cognitive dysfunction. Multivariate logistic regression analysis was applied to assess the independent predictors associated with cognitive function impairment. A total of 76 patients were recruited, 10 patients were excluded due to refusal or unable to finish the questionnaire, and 66 patients were analyzed in this study. The median age of the patients was 48.5 years (range, 24-69 years). There was 89.4% of patients received ≥3 circles of IC. For the entire group, 27.3% had cognitive dysfunction, of which attention, language, short-term memory, and orientation showed significant downward trends, while visuospatial/executive function, naming, and abstraction demonstrated no prominent decrease. In patients having cognitive function impairment, 77.8% of them occurred after the first circle of IC. Gender (P = 0.039) and education (P = 0.03) were significant predictors for cognitive dysfunction. Female patients (female vs. male: 50% vs. 20%) and patients with lower educational levels (lower vs. higher: 37.8% vs. 11.8%) were more likely to suffer cognitive dysfunction. In addition, age (P = 0.572) and chemotherapy circles (P = 0.68) had no association with cognitive dysfunction. Approximately 25% of NPC patients suffered cognitive dysfunction after IC, especially in female patients and patients with lower educational levels.
Pubmed PDF WebMingming Lv, Xin Yang, Anand Gupta, Yi Shen, Jun Li, Jian Sun
Publicatie 08-08-2020
The aim of this article is to introduce and share our experience in the sequential use of a novel guiding plate system for accurate mandibular reconstruction via transoral approach and evaluate its clinical effects. Ten patients were operated with transoral mandibulectomy and simultaneous mandibular reconstruction using a novel guiding plate system. Postoperatively, aesthetic assessment and quantitative evaluation were analyzed by measuring the parameters like discrepancy in osteotomy lines, mandibular similarity and symmetry. The independent samples t-test was used and P < 0.05 was considered as significant. All patients underwent planned transoral surgical procedure successfully. The postoperative aesthetic assessment was rated as excellent. The discrepancy between virtual and actual osteotomy lines, at anterior and posterior regions was 0.80 ± 0.08 and 0.98 ± 0.37 mm, respectively. The postoperative evaluation revealed that mandibular similarity was 0.85 ± 0.03, coronal mandibular angle (CMA) 0.66 ± 0.40, axial mandibular angle (AMA) 1.97 ± 1.25, and sagittal mandibular angle (SMA) 1.97 ± 1.05. There was statistically significant difference in the mean values of osteotomy line discrepancy, mandibular similarity and symmetry, among novel guiding plate and traditional plate groups. The novel guiding plate system is a viable and easy-to-use technology for improving the surgical outcomes in patients requiring transoral mandibulectomy and simultaneous mandibular reconstruction by overcoming the problem of limited access due to the presence of lips and cheeks. This can highly improve the precision in osteotomy, fixation of the prebent titanium reconstruction plate, spatial relation transfer, and achieving better symmetry and similarity of mandibular contour.
Pubmed PDF WebDavide Mattavelli, Marco Ferrari, Stefano Taboni, Riccardo Morello, Alberto Paderno, Vittorio Rampinelli, Francesca Del Bon, Davide Lombardi, Alberto Grammatica, Paolo Bossi, Alberto Deganello, Cesare Piazza, Piero Nicolai
Publicatie 05-08-2020
The 8th TNM edition remarkably changed the classification of T and N categories for oral squamous cell carcinoma (OSCC). The present study aims at evaluating the improvement in prognostic power compared to the 7th edition, pros and cons of the modifications, and parameters deserving consideration for further implementations. All OSCCs treated with upfront surgery at our institution between 2002 and 2017 were included. Demographics, clinical-pathological and treatment variables were retrieved. All tumors were classified according to both the 7th and 8th TNM edition, and patients were grouped according to the shift in T category and stage. Survivals were calculated with the Kaplan-Meier method. Univariate and multivariate analysis were carried out. Receiver Operating Characteristics (ROC) curve analyses were performed to find the best cut-off of DOI (in patients with DOI > 10 mm) and number of involved nodes (in positive neck patients). 244 patients were included. T, N categories, and stage changed in 59.2%, 20.5%, and 49.1% patients, respectively; 41.5% of patients were upstaged. The new T classification well depicted prognosis according to OS. Five-year overall (OS), disease-specific, recurrence-free (RFS) survivals were 60.5%, 70.9%, 59.8%, respectively. According to ROC curves, DOI > 20 mm and 4 positive nodes were the best cutoffs for OS and RFS. The novelties introduced in 8th TNM edition were positive. DOI > 20 mm for T4 definition and number of positive nodes (0, <4, 4 or more) for N classification emerged as the most urgent factors to be implemented.
Pubmed PDF WebBogusław Mikaszewski, Karolina Markiet, Aneta Smugała, Dominik Stodulski, Edyta Szurowska, Czesław Stankiewicz
Publicatie 03-08-2020
To verify if differential diagnostic algorithms based on selected parameters of dynamic and diffusion-weighted MRI, clinical and demographic variables are accurate enough to differentiate between parotid malignancies, pleomorphic adenomas and Warthin tumors. The study included 84 patients, among them 19 (23%) with postoperative diagnosis of a parotid malignancy, 37 (44%) with Warthin tumors and 28 (33%) with pleomorphic adenomas. Accuracy of dynamic and diffusion-weighted MRI parameters (T Compared to Warthin tumors, parotid malignancies showed higher T Combined analysis of clinical data and results of dynamic and diffusion-weighted MRI may provide nearly ideal accuracy in differential diagnostics of parotid malignancies and the two most common histological types of benign tumors.
Pubmed PDF WebArjun Singh, Aseem Mishra, Hitesh Singhvi, Florida Sharin, Munita Bal, Sarbani Ghosh Laskar, Kumar Prabhash, Pankaj Chaturvedi
Publicatie 03-08-2020
To evaluate the impact of progressively increasing margin distances on locoregional recurrence-free survival (LFRS) and determine an optimum margin distance for tongue cancers. We retrospectively reviewed the records of patients with squamous carcinoma of oral tongue, surgically treated between January 2012 and December 2013. The patients were divided based on ROC derived optimal distance and differences in LRFS per millimeter: margin distances with no significant difference in LRFS starting from 0 mm onwards (Group-I), from upper limit of Group-I to ROC cut-off (Group-II), and all values above it (Group-III). Group-II and III were matched for clinicopathologic factors and type of adjuvant therapy received. 451 patients had a median LRFS of 29.4 months that included 32.1% of Stage I/II and 51.7% of Stage III/IV. Group-I consisted of 0--2.0 mm (2.0-2.1 mm (p-0.029)), Group-II form 2.1 to 7.5 (7.5-7.6 mm (p-0.042)) and Group-III were ≥ 7.6 mm. In the matched group, each millimeter increase in margin provided a 3.67 months survival advantage from 2.1 mm to 7.5 mm while a substantial advantage of 15 months was seen from 7.5 to 7.6 mm. No significant advantage was gained in LRFS when the margin was increased by a millimeter from the cut-off value (p-0.602). Among the patients that were not prescribed any adjuvant therapy, a significantly better LRFS was observed in Group III than Group II (HR-3.01, p-value = 0.002). Based on these results, adequacy of surgical margins should be re-considered for oral tongue cancers.
Pubmed PDF WebDerrick Lin, Brian Lin, Haymanti Bhanot, Rozenn Riou, Nicholas B. Abt, Jayaraj Rajagopal, Srinivas Vinod Saladi
Publicatie 04-08-2020
Mutations in histone modifying enzymes and histone variants were identified in multiple cancers in The Cancer Genome Atlas (TCGA) studies. However, very little progress and understanding has been made in identifying the contribution of epigenetic factors in head and neck squamous cell carcinoma (HNSCC). Here, we report the identification of RUVBL1 (TIP49a), a component of the TIP60 histone modifying complex as being amplified and overexpressed in HNSCC. RUVBL1 plays a key role in incorporating histone variant H2AZ in chromatin thereby regulating transcription of key genes involved in differentiation, cancer cell proliferation and invasion. H2AZ is also overexpressed in HNSCC tumors thereby regulating RUVBL1/H2AZ dependent transcriptional programs. Patient data analysis of multiple cohorts including TCGA and single cell HNSCC data indicated RUVBL1 overexpression as a poor prognostic marker and predicts poor survival. In vitro experiments indicate a pro-proliferative role for RUVBL1/H2AZ in HNSCC cells. RUVBL1 inversely correlates with differentiation program and positively correlates with oncogenic programs, making it a key contributor to tumorigenesis and a vulnerable therapeutic target in HNSCC patients.
Pubmed PDF WebGregory T. Wolf, Siyu Liu, Emily Bellile, Maureen Sartor, Laura Rozek, Dafydd Thomas, Ariane Nguyen, Katie Zarins, Jonathan B. McHugh, Jeff Moyer, Mihir Patel, Nabil Saba, Audrey Erman, Wanessa A. Martins, Jason G. Newman, Michael Kaplan, Frabicio Oliveira, Ana Paula Victorina, R. Bryan Bell, Gustavo C. Girotto
Publicatie 02-08-2020
IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT02609386).
Pubmed PDF WebNikolina Kesar, Ria Winkelmann, Julius Oppermann, Shahram Ghanaati, Daniel Martin, Thomas Neumayer, Sven Balster, Claus Rödel, Franz Rödel, Jens von der Grün, Panagiotis Balermpas
Publicatie 01-08-2020
Aim of the study was to evaluate the prognostic impact of CD8-positive (CD8 Formalin-fixed, paraffin-embedded tissue samples and clinicopathological data from patients treated for salivary gland carcinoma in a head and neck cancer centre were retrospectively retrieved. Immunohistochemical staining was applied on sections of 84 specimens of 12 different histological subtypes. Both CD8 and PD-L1 expression were rated by semi-automated cell counts by a digital image analysis programme. Survival analyses were performed by the log-rank test on the univariate level, and the Cox model was applied on the multivariate level. Associations between immunological markers and clinicopathological variables were estimated by the Pearson chi-squared test. Additionally, PD-1 was estimated as an exhaustion marker of CD8 Patients exceeding a tumour proportion score ≥5% regarding PD-L1 expression demonstrated a significantly decreased survival, as did individuals with an overall high CD8 CD8
Pubmed PDF WebYuan-Yuan Zeng, Zhong-Zheng Xiang, Tao He, Fang Liu, Bian-Fei Shao, Ruo-Nan Yan, Jia-Chun Ma, Xi-Ran Wang, Lei Liu
Publicatie 01-08-2020
To compare the prognostic value of the sum volumetric regression ratio (SVRR) of the primary tumour and metastatic lymph nodes with treatment response based on RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 117 stage III-IVA NPC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) were retrospectively reviewed. The SVRR and the treatment response based on RECIST 1.1 were measured using contrast-enhanced computed tomography (CT) localisations before and after induction chemotherapy. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff point of the SVRR and compare the prognostic value of the SVRR and RECIST 1.1criteria. The optimal cutoff points of SVRR for progression-free survival (PFS), locoregional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were all 25.15%, while for overall survival (OS) it was 16.63%. The area under the ROC curve (AUC) of optimal cutoff points of SVRR was superior than that of RECIST 1.1 for PFS (AUC: 0.716 vs. 0.578; P = 0.0022), LRFFS (AUC: 0.700 vs. 0.574; P = 0.0080) and DMFS (AUC: 0.736 vs. 0.606; P = 0.0053), respectively. The 3-year PFS, DMFS and OS rates for SVRR less than vs. greater than or equal to the cutoff points were 55.8% vs. 92.2% (P < 0.001, hazard ratio (HR): 0.209, 95% confidence interval (CI): 0.091-0.480), 59.7% vs. 96.7% (P < 0.001, HR: 0.120, 95% CI: 0.043-0.336) and 66.7% vs. 98.1% (P < 0.001, HR: 0.069, 95% CI: 0.014-0.342), while the responses [stable disease (SD), partial response (PR)] based on RECIST 1.1 were not significantly associated with 3-year survival rates. Multivariate analysis indicated that SVRR was an independent prognostic factor for PFS, DMFS and OS (all P < 0.05). The sum volumetric regression ratio and response based on RECIST 1.1 were related to the prognosis in locoregionally advanced NPC after induction chemotherapy. Sum volumetric regression ratio is an independent outcome predictor for survival in locoregionally advanced NPC, playing a better prognostic role than RECIST 1.1.
Pubmed PDF WebSamantha Tam, Wenli Dong, David M. Adelman, Randal S. Weber, Carol M. Lewis
Publicatie 30-07-2020
With the current focus on value-based outcomes and reimbursement models, perioperative risk adjustment is essential. Specialty surgical outcomes are not well predicted by the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP); the Head and Neck-Reconstructive Surgery NSQIP was created as a specialty-specific platform for patients undergoing head and neck surgery with flap reconstruction. This study aims to investigate risk prediction models in these patients. The Head and Neck-Reconstructive Surgery NSQIP collected data on patients undergoing head and neck surgery with flap reconstruction from August 1, 2012 to October 20, 2016. Multivariable logistic regression models were created for 9 outcomes (postoperative ventilator dependence, pneumonia, superficial recipient surgical site infection, presence of tracheostomy/nasoenteric (NE)/gastrostomy/gastrojejunostomy(G/GJ) tube 30 days postoperatively, conversion from NE to G/GJ tube, unplanned return to the operating room, length of stay > 7 days). External validation was completed with a more contemporary cohort. A total of 1095 patients were included in the modelling cohort and 407 in the validation cohort. Models performed well predicting tracheostomy, NE, G/GJ tube presence at 30 days postoperatively and conversion from NE to G/GJ tube (c-indices = 0.75-0.91). Models for postoperative pneumonia, superficial recipient surgical site infection, ventilator dependence > 48 h, and length of stay > 7 days were fair (concordance [c]-indices = 0.63-0.69). The predictive model for unplanned return to the operating room was poor (c-index = 0.58). Reliable and discriminant risk prediction models were able to be created for postoperative outcomes using the specialty-specific Head and Neck-Reconstructive Surgery Specific NSQIP.
Pubmed PDF WebKathryn M. Van Abel, David M. Routman, Eric J. Moore, Daniel J. Ma, Linda X. Yin, Paul A. Fields, Matt Schofield, Kathleen R. Bartemes, Kyriakos Chatzopoulos, Daniel L. Price, Jeffrey R. Janus, Jan L. Kasperbauer, Katharine A. Price, Ashish V. Chintakuntlawar, Michelle A. Neben-Wittich, Robert L. Foote, Joaquin J. Garcia
Publicatie 28-07-2020
We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. This nested case-control study included patients undergoing intent-to-cure surgery ± adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains. 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p > 0.05). Female sex was associated with higher TCF (p = 0.03), while extranodal extension (ENE) was associated with lower TCF (p = 0.01). There was a positive correlation between tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p = 0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p = 0.01) and ACE-27 score (p = 0.03). On multivariable modeling, TCF ≥ 0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p = 0.02) while an ACE-27 score of ≥ 2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p = 0.03). In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.
Pubmed PDF WebWanpeng Li, Hanyu Lu, Juan Liu, Quan Liu, Huan Wang, Huankang Zhang, Li Hu, Weidong Zhao, Yurong Gu, Houyong Li, Xicai Sun, Dehui Wang
Publicatie 28-07-2020
To develop and validate a nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma (NPC) after salvage endoscopic surgery. A total of 229 eligible patients with recurrent NPC were divided into training (n = 115) and validation (n = 114) cohorts. A multivariate Cox proportional risk regression model was used to identify significant prognostic factors for overall survival (OS) in the training cohort. A nomogram was then developed based on the regression model. The performance of the nomogram was assessed with regard to discrimination and calibration. Patients were divided into low-risk or high-risk groups based on the risk scores derived from the nomogram. Furthermore, decision curve analysis (DCA) was used to assess the clinical utility of the nomogram. Six significant predictors were identified: diabetes mellitus, body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), T stage, lymph node metastasis, and tumor necrosis. The nomogram incorporating these six predictors demonstrated favorable discrimination and calibration in the training cohort, with a C-index of 0.746 (95% confidence interval [CI] 0.656-0.836), which was subsequently confirmed in the validation cohort (C-index 0.768 [95% CI 0.675-0.861]). Furthermore, the nomogram successfully distinguished patients into low- and high-risk groups. DCA indicated that the nomogram was clinically useful. The novel nomogram demonstrated its potential as an individual tool to predict survival in patients with recurrent NPC after salvage endoscopic surgery.
Pubmed PDF WebJingya Jane Pu, Wing Shan Choi, Peirong Yu, May Chun Mei Wong, Anthony W.I. Lo, Yu-Xiong Su
Publicatie 28-07-2020
Computer assisted head and neck reconstruction has gained popularity over the past few years. In computer assisted surgery (CAS), surgical margins are predetermined in virtual surgery and resection guides are designed to be fitted intra-operatively. However, concerns have been raised regarding the oncological safety of predetermined surgical margins. Therefore, the aim of this study was to compare surgical margins, recurrence and survival outcomes in patients underwent CAS and non-CAS in head and neck reconstruction. We retrospectively reviewed the patients underwent oral and maxillofacial malignancies surgical excision and free flap reconstruction from October 2014 to December 2019 by the same chief surgeon. Patients were divided into two groups depending on whether CAS and predetermined surgical margins were adopted. The primary outcome was surgical resection margin and the secondary outcomes included recurrence and survival. A total of 66 subjects were recruited with 37 in the CAS group and 29 in the non-CAS group. The follow-up rate was 100%. The average follow-up time was 24.5 months. No significant difference in resection margin was identified between the groups (p = 0.387). Tumor staging, margin status, perineural invasion, lymphovascular invasion and extranodal extension were identified as significant factors influencing survival. Both before and after adjustment for these prognostic factors identified, CAS and non-CAS group showed no significant difference in survival outcome. Predetermined surgical margins do not compromise oncological safety in terms of resection margin, disease recurrence and patient survival.
Pubmed PDF WebTejpal Gupta, Sarbani Ghosh-Laskar, Jai Prakash Agarwal
Publicatie 23-10-2020
The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income countries (LMICs) with resource-constraints. Loco-regional recurrence remains the predominant pattern of failure mandating adequate local therapy for acceptable loco-regional control and survival. There is high-quality evidence that intensification of treatment by either by adding concurrent chemotherapy or by altering radiotherapy (RT) fractionation improves outcomes in the curative-intent management of loco-regionally advanced HNSCC. Even conservative estimates indicate that >50% of patients in LMIC are unlikely to get access to timely RT, which will only get compounded with the coronavirus disease (COVID)-19 pandemic. The radiation oncology community has been systematically testing altered fractionation schedules in several solid cancers (breast, lung, and head-neck), given the cost-effectiveness, convenience, and compliance to short-course RT regimens. Radiobiological modelling suggests that standard fractionation of 6-7 weeks in HNSCC can be compressed safely into a 4-week schedule to counter accelerated repopulation by increasing the dose per fraction and delivering 5 fractions per week which is currently being tested in the ongoing multicentric trial of hypo- vs normo-fractionated accelerated RT (HYPNO study). Herein, we discuss the radiobiological basis of curative-intent hypofractionated-accelerated RT schedule delivering 55 Gy in 20 fractions over 4 weeks in HNSCC followed by critical appraisal of the published literature on such regimens with concurrent systemic therapy and its inherent resource-sparing potential applicable across large parts of the world particularly in the context of the ongoing COVID-19 pandemic.
Pubmed PDF WebRemo Accorona, Alessandra DOnghia, Lorenzo Pignataro, Pasquale Capaccio
Publicatie 04-08-2020
Robotic approaches and sentinel lymph node (SLN) biopsy are both strategies that evolved driven by the need to reduce impact of head and neck oncological surgery in terms of operative timing, morbidity, hospitalization time, and aesthetic results. A comprehensive review of the scientific literature was performed on PubMed, Embase, ResearchGate, Cochrane, and CENTRAL electronic databases with the aim to discuss the role that these two approaches can play together in the management of head and neck cancers (HNCs) of various sites. Dedicated publications on the combined robotics and SLN biopsy approaches resulted, up to now very limited, while their separated application in non-shared fields is gaining strength. However, the possibility to implement and combine technologies to minimize sequelae of head and neck surgery is an interesting and evolving topic.
Pubmed PDF WebQiaoli Wang, Guoqiang Xu, Yaoxiong Xia, Jia Zuo, Guilin Zeng, Zhihong Xue, Ruixue Cao, Wei Xiong, Wenhui Li
Publicatie 30-07-2020
Induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) is a standard treatment regimen for locally advanced nasopharyngeal carcinoma (LA-NPC). However, the increased acute toxicity of this intensified chemotherapy may counteract its efficacy. The results of studies focusing on the omission of concurrent chemotherapy (CC) regimens are controversial. Therefore, we carried out a meta-analysis to elucidate the efficacy and toxicity of IC + CCRT versus IC plus radiotherapy alone (IC + RT) for LA-NPC. Studies available on PubMed, Embase, Cochrane Library and ClinicalTrails.gov were independently searched by two investigators from inception to March 1, 2020. Review Manager software 5.3 (RevMan 5.3) was employed to calculate pooled hazard ratios (HRs), risk ratios (RRs) and 95% confidence intervals (CIs). Eight studies with a total of 2605 patients were analysed. The results showed that no significant difference between IC + RT and IC + CCRT for disease-free survival (HR = 1.09, 95% CI: 0,85-1.39, P = 0.50), overall survival (HR = 0.92, 95% CI: 0.78-1.09, P = 0.34), local recurrence-free survival (HR = 1.26, 95% CI: 0.95-1.67; P = 0.10), or distant metastasis-free survival (HR = 1.03, 95% CI: 0.84-1.26, P = 0.79). Notably, the incidence of treatment-related grade 3/4 acute haematological toxicity during radiation was higher in the IC + CCRT group. Subgroup analysis showed similar survival outcomes for IC + CCRT and IC + RT with and without the two-dimensional RT technique. IC + RT was as effective as IC + CCRT for the management of LA-NPC. The IC + RT regimen has the possibility of replacing the IC + CCRT regimen for LA-NPC in the future due to the lower toxicity, although more high-level evidence is urgently needed for verification.
Pubmed PDF WebWendy DSouza, Arun Kumar
Publicatie 28-07-2020
Oral cancer is the thirteenth most common cancer in the world, with India contributing to 33% of the global burden. Lack of specific non-invasive markers, non-improvement in patient survival and tumor recurrence remain a major clinical challenge in oral cancer. Epigenetic regulation in the form of microRNAs (miRs) that act as tumor suppressor miRs or oncomiRs has gained significant momentum with the advancement in the field, suggesting the potential for clinical application of miRs in oral cancer. The current review of literature identified miR-21, miR-27a(-3p), miR-31, miR-93, miR-134, miR-146, miR-155, miR-196a, miR-196b, miR-211, miR-218, miR-222, miR-372 and miR-373 to be up-regulated and let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, miR-26a, miR-99a-5p, miR-137, miR-139-5p, miR-143-3p, miR-184 and miR-375 to be down-regulated in oral cancer. Mechanistic studies have uncovered several miRs that are deregulated at varying levels and in different stages of oral cancer progression, thus providing clinical utility in better diagnosis as well as usefulness in prognosis by identifying patients with poor prognosis or stratifying patients based on responsiveness to chemo- and radio-therapy. Lastly, exogenous modulation of miR expression using miRNA-based drugs in combination with first-line agents may be adopted as a new therapeutic modality to treat oral cancer. Knowledge of miRs and their involvement in key molecular processes, clinical association, responsiveness to therapy and clinical advancement may highlight additional avenues in order to improve patient morbidity and mortality. Furthermore, combinatorial approaches with miR-therapy may be efficacious in oral cancer.
Pubmed PDF WebJeremy Chee, Xinyi Lin, Wei Sian Lim, Woei Shyang Loh, Mark Thong, Lishia Ng
Publicatie 13-10-2020
The COVID-19 pandemic has swept across the globe with massive effects on health care systems as well as global economies. Enhanced testing has been put forward as a means to reduce transmission while awaiting the development of targeted therapy or effective vaccination. However, achieving accurate testing necessitates proper nasopharyngeal swab techniques. We aimed to design and investigate the utility of an anatomically accurate three-dimensional (3D) printed model of the nose in the training for nasopharyngeal swabs. These models were implemented during training sessions for healthcare workers. All participants surveyed felt that the 3D printed models were useful and beneficial in the training of nasopharyngeal swab techniques. 3D printed nose models are a useful tool in nasopharyngeal swab training. Their usage may help to facilitate the training of potential swabbing manpower in the upscaling of testing capabilities and volumes in this COVID-19 era.
Pubmed PDF WebMolly E. Heft Neal, Rebecca W. Gao, Julia R. Brennan, Catherine T. Haring, Steven B. Chinn, Andrew G. Shuman, Keith A. Casper, Kelly M. Malloy, Chaz L. Stucken, Scott A. Mclean, J. Chad Brenner, Teresa Lyden, Anna Blakely, Michelle L. Mierzwa, Jennifer Shah, Caitlin Schonewolf, Paul L. Swiecicki, Frank P. Worden, Gregory T. Wolf, Carol R. Bradford
Publicatie 13-10-2020
Miguel Ángel González-Moles, Saman Warnakulasuriya, Isabel González-Ruiz, Lucía González-Ruiz, Ángela Ayén, Daniel Lenouvel, Isabel Ruiz-Ávila, Pablo Ramos-García
Publicatie 13-10-2020
Valentina Terenzi, Andrea Battisti, Marco Della Monaca, Paolo Priore, Edoardo Brauner, Silvia Mezi, Francesca De Felice, Daniela Musio, Vincenzo Tombolini, Antonella Polimeni, Valentino Valentini
Publicatie 12-10-2020
Barbara Burtness, Joy Ge
Publicatie 10-10-2020
Narayana Subramaniam, Sujan K. Dhar, Roopa Rao, Kavitha Prasad, Manjula Das
Publicatie 06-10-2020
Katarzyna Lammek, Dmitry Tretiakow, Andrzej Skorek
Publicatie 04-10-2020
Dongliang Wei, Dongsheng Chen, Si Li, Jing Tian, Guoxin Ren
Publicatie 04-10-2020
Dmitry Tretiakow, Dominik Stodulski, Boguslaw Mikaszewski
Publicatie 30-09-2020
José Alcides Almeida de Arruda, Ricardo Alves Mesquita, Nathalie Henriques Silva Canedo, Michelle Agostini, Aline Corrêa Abrahão, Bruno Augusto Benevenuto de Andrade, Mário José Romañach
Publicatie 30-09-2020
Merkel cell carcinoma (MCC) is an aggressive primary cutaneous neuroendocrine carcinoma that predominantly affects the sun-damaged skin of the head and neck region, extremities, and trunk of white older individuals. Microscopically, small to intermediate round blue cells show granular nuclei with a salt-and-pepper chromatin pattern, and are usually positive for epithelial and neuroendocrine markers, particularly for cytokeratin 20 in a perinuclear dot-like staining. The 5-year overall survival rate for individuals with localized MCC is 51% and the most common treatment choice is surgery with adjuvant radiotherapy. As far as we know, 23 cases of MCC of the lips have been reported to date in the English-language literature. We herein contribute by reporting a case of MCC affecting the lower lip of an 81-year-old male patient from Rio de Janeiro, Brazil, which likely represents the first reported case from Latin America. A review of the current literature is also included in an effort to familiarize providers with this rare, but potentially lethal neuroendocrine tumor.
Pubmed PDF WebAnalú Barros de Oliveira, Túlio Morandin Ferrisse, Heitor Albergoni Silveira, Evanio Vilela Silva, Andreia Bufalino, Jorge Esquiche León, Fernanda Lourenção Brighenti
Publicatie 30-09-2020
We present a rare case of intraoral atypical lentiginous melanocytic lesion affecting a pediatric patient, in which the diagnosis of lentiginous junctional melanocytic nevus with cytologic atypia was favored. The main differential diagnosis is lentiginous melanoma, which is a slowly progressing lesion, affecting mainly older adults, and microscopically presenting lentiginous growth pattern of moderately atypical melanocytes, with focal nesting and pagetoid spread. It is strongly recommended that melanocytic lesions showing features of atypical lentiginous growth pattern should be treated with wide excision; however, the impact of these guidelines on pediatric patients needs to be better defined with the report of further cases.
Pubmed PDF WebChristian Camenzuli, Pierre Schembri Wismayer, Jean Calleja Agius
Publicatie 29-09-2020
Piotr Nogal, Ewelina Bartkowiak, Katarzyna Iwanik, Małgorzata Wierzbicka
Publicatie 26-09-2020
Pilomatrical carcinoma is a rare tumor originating from skin appendages, usually occurring between the 5th and 7th decade of life. We present a case of an exceptionally young, 21-year-old patient with surprisingly rapid tumor progression and answer the question, what was the reason for such uncontrolled tumor growth. The main concern is the diagnostic challenge and a peculiar, one week race against time and tumor progression so that the least disfiguring surgery could be done.
Pubmed PDF WebÓscar Rapado-González, Laura Muinelo-Romay, María Mercedes Suárez-Cunqueiro
Publicatie 26-09-2020
Stephanie Flukes, Shivangi Lohia, Christopher A. Barker, Jennifer R. Cracchiolo, Ian Ganly, Snehal G. Patel, Benjamin R. Roman, Jatin P. Shah, Alexander N. Shoushtari, Viviane Tabar, Marc A. Cohen
Publicatie 23-09-2020
Yuyan Jiao, Ming Liu, Ningning Luo, Hao Guo, Jianzhe Li
Publicatie 19-09-2020
Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung carcinoma (NSCLC), which characterized by insensitive to conventional radiotherapy and chemotherapy and poor prognosis. Except MET exon 14 alterations and other oncogene mutations, PSC commonly harbor high tumor mutational burden (TMB) and high level of PD-L1, which provide new therapeutic opportunities. Toripalimab (JS001) is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy. PD-1 combined with radiotherapy has been tried in several cancer types. We reported a case of a PSC patient with PD-L1 overexpression responding to toripalimab and after progression the patients also benefits from toripalimab combined with local radiotherapy, which provides a promising option for PSC patients. This case provides the evidence of the effective role of toripalimab and PD-1 combined with local radiotherapy in PSC patients, which was the first application as far as we know.
Pubmed PDF WebMingbo Wang, Fuxin Zhu, Ningning Luo, Tiantian Han, Musen Wang
Publicatie 06-09-2020
MUTYH-associated polyposis (MAP) is an autosomal recessively inherited disease with multiple system tumors mainly in alimentary system. Tumor occurrence of MAP patients is highly heterogeneous in space and time. MAP is associated with germline biallelic mutations in MUTYH. The targeted next‑generation sequencing technology and Sanger sequencing are the important methods to screen MUTYH mutations now. Herein, we identified a patient with heterochronous multiprimary tumor carring MUYTH Arg19*/Gly286Glu compound heterozygous mutations. The patient in this case had a first phenotype of thyroid cancer at age 44, which earlier 2 years than the alimentary system cancers. In conclusion, our case report creases the in-depth understanding of the MAP heterogeneous phenotype and further reminds recommendations for improvement of health management and genetic counseling, special treatment plans.
Pubmed PDF WebRuth Gabriela Herrera Gómez, Khalil Saleh, Lamia Mayache, Mariana Iacob, Neus Baste, Caroline Even
Publicatie 06-09-2020
Marie Martin, Brieuc Sautois
Publicatie 06-09-2020
Sandeep Bhoriwal, Jyoti Sharma, Kunal Dhall, Amitabha Mandal, Madiwalesh Chhebbi, T.S.H.V. Surya
Publicatie 06-09-2020
Konstantinos Mantsopoulos, Heinrich Iro
Publicatie 03-09-2020
Intraoperative rupture of a pleomorphic adenoma capsule with potential tumor spillage into the surgical field is thought to occur in approximately 5% of cases and has traditionally been recognized as one of the major causes of recurrence. It seems that recurrence of a pleomorphic adenoma is a multifactorial event, being related to surgery (capsular exposure, tumor spillage) and tumor-related factors (histologic subtype, incomplete capsule, pseudopodia, satellites). The exact quantities of these ingredients in the recipe of recurrence, as well as possible interactions between them (e.g. the potentially increased fragility of myxoid pleomorphic adenomas; satellites or pseudopodia being cut off the tumor specimen during an extremely narrow extracapsular dissection) remain unclear. A thorough literature search did not reveal any proposed algorithms for the intraoperative management of a capsular tear. The aim of this short communication is to present our department's experience-based proposal for intraoperative measures in the case of macroscopic rupture and tumor spillage of a parotid gland pleomorphic adenoma.
Pubmed PDF WebCarole Fakhry, Nicholas Fung, Sakshi R. Tewari, Gypsyamber DSouza
Publicatie 03-09-2020
Yash P. Merchant, Anand Subash, Sameep Shetty, Abhijith George, Akshay Kudpaje, Vishal U.S. Rao
Publicatie 31-08-2020
A. Singh, C.A. Singh, K. Sikka
Publicatie 26-08-2020
Prashanth Panta
Publicatie 25-08-2020
Dongliang Wei, Dongsheng Chen, Lijian Li, Jing Tian, Guoxin Ren
Publicatie 23-08-2020
Itisha Chaudhary, Mahesh Sultania, Pavithra Ayyanar, Pritinanda Mishra, Amit Kumar Adhya, Dillip Kumar Muduly, Madhabananda Kar
Publicatie 10-08-2020
B. Vigneshwaran, Swagatika Samal, Mukund Namdev Sable, Amit Kumar Adhya, DillipKumar Muduly, Madhabanada Kar, Boyina Kiran Kumar, Mahesh Sultania
Publicatie 29-07-2020