Oral Oncology 2020-09-14

Optimum surgical margins in squamous cell carcinoma of the oral tongue: Is the current definition adequate?

Arjun 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.

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Number of nodal metastases and the American Joint Committee on cancer staging of head and neck cutaneous squamous cell carcinoma: A multicenter study

Ardalan 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.

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Characterization of very late dysphagia after chemoradiation for oropharyngeal squamous cell carcinoma

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.

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Long-term outcomes of patients in different histological subtypes of primary nasopharyngeal adenocarcinoma: A single-center experience with 71 cases

Meng 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.

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Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients

Christina 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.

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Slug is a novel molecular target for head and neck squamous cell carcinoma stem-like cells

Jung 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.

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Depth of invasion in early stage oral cavity squamous cell carcinoma: The optimal cut-off value for elective neck dissection

Cornelia 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.

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HOXC13-AS accelerates cell proliferation and migration in oral squamous cell carcinoma via miR-378g/HOXC13 axis

Wenlu 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.

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The differences of immunologic and TP53 mutant phenotypes between synchronous and metachronous head and neck cancer and esophageal cancer

Tseng-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.

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Cognitive dysfunction in patients with nasopharyngeal carcinoma after induction chemotherapy

Jun 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.

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Sequential application of novel guiding plate system for accurate transoral mandibular reconstruction

Mingming 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.

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The 8th TNM classification for oral squamous cell carcinoma: What is gained, what is lost, and what is missing

Davide 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.

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Clinical and demographic data improve diagnostic accuracy of dynamic contrast-enhanced and diffusion-weighted MRI in differential diagnostics of parotid gland tumors

Bogusław 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.

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Corrigendum to “Imaging in oral cancers: A comprehensive review” Oral Oncol. 104 (2020) 104658

Abhishek Mahajan, Ankita Ahuja, Nilesh Sable, Hilda E. Stambuk

Publicatie 21-08-2020


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RUVBL1 is an amplified epigenetic factor promoting proliferation and inhibiting differentiation program in head and neck squamous cancers

Derrick 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.

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Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial

Gregory 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).

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Prognostic impact of CD8-positive tumour-infiltrating lymphocytes and PD-L1 expression in salivary gland cancer

Nikolina 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

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The comparison of prognostic value of tumour volumetric regression ratio and RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

Yuan-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.

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Risk-adjustment models in patients undergoing head and neck surgery with reconstruction

Samantha 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.

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T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma

Kathryn 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.

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A novel nomogram to predict survival in patients with recurrent nasopharyngeal carcinoma after salvage endoscopic surgery

Wanpeng 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.

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Do predetermined surgical margins compromise oncological safety in computer-assisted head and neck reconstruction?

Jingya 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.

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Head and neck robotic surgery combined with sentinel lymph node biopsy. Fascinating, but feasible?

Remo 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.

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Comparison of induction chemotherapy plus concurrent chemoradiotherapy and induction chemotherapy plus radiotherapy in locally advanced nasopharyngeal carcinoma

Qiaoli 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.

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microRNAs in oral cancer: Moving from bench to bed as next generation medicine

Wendy 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.

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Functional and survival outcomes in elderly patients undergoing transoral robotic surgery

Ramez 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.

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The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study

Lizao Zhang, Bowen Li, Yu Peng, Fan Wu, Qunxing Li, Zhaoyu Lin, Shule Xie, Liping Xiao, Xinyu Lin, Zhanpeng Ou, Tingting Cai, Haixu Rong, Song Fan, Jinsong Li

Publicatie 13-09-2020


Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC). TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups. High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients. HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration.

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Prognostic value of prognostic nutritional index in nasopharyngeal carcinoma: A meta-analysis containing 4511 patients

Xiaomin Tu, Jianjun Ren, Yu Zhao

Publicatie 13-09-2020


The prognostic nutritional index (PNI) is an index reflecting the nutritional and inflammatory status of patients and is explored for prognosis in nasopharyngeal carcinoma (NPC). However, the data are conflicting. In the current study, a meta-analysis was performed to comprehensively clarify the association between PNI and prognosis of NPC. PubMed, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), and Wanfang database were searched up to July 25, 2020. Hazard ratio (HR) and with 95% confidence interval (CI) were calculated to assess the impact of PNI on the survival outcomes of patients with NPC. A total of 10 studies containing with 4511 patients were identified. The pooled results showed that NPC patients with a low PNI would have a worse overall survival (OS) (HR = 1.89, 95%CI = 1.59-2.25, p < 0.001), distant metastasis-free survival (DMFS) (HR = 2.01. 95%CI = 1.66-2.43, p < 0.001), progression-free survival (PFS) (HR = 1.59, 95%CI = 1.32-1.91, p < 0.001), and locoregional recurrence-free survival (LRRFS) (HR = 1.51, 95%CI = 1.04-2.21, p = 0.032). Subgroup analysis showed that the low PNI was still a significant prognostic factor for OS and DMFS. Our meta-analysis demonstrated that a low PNI was significantly correlated to poor OS, DMFS, PFS, and LRRFS in NPC. Therefore, we suggest PNI applied as an indicator for prediction of the short- and long- term survival outcomes in patients with NPC.

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Validation of local p16 testing for determination of human papilloma virus status eligibility on a low risk oropharyngeal cancer trial – A Trans-Tasman Radiation Oncology Group study

Richard J. Young, Benjamin Solomon, June Corry, Christopher Angel, Lizbeth Kenny, Sandro Porceddu, Christopher Wratten, Andrew Macann, James E. Jackson, Alan Herschtal, Danny Rischin

Publicatie 06-09-2020


Accurate determination of human papilloma virus (HPV) status is critical when identifying patients with oropharyngeal squamous cell carcinoma (OPSCC) who may be candidates for de-escalation trials. In this study we investigated whether local p16 screening, by immunohistochemistry (IHC), has high positive predictive value (PPV) for HPV status in a good prognosis HPV positive OPSCC (HPVOPSCC) population treated on a clinical trial. Patients enrolled on the TROG 12.01 randomised trial for good prognosis HPVOPSCC were randomised based on local p16 IHC testing but subsequently had central p16 IHC and HPV RNA in situ hybridisation (HPV RNA ISH) testing. Correlations between the local and central p16 and central HPV RNA ISH were studied. The main outcome was the positive predictive value (PPV) of local pathology laboratory testing of p16. 176/182 patients had samples available for central testing. 172/176 were evaluable for central testing of p16, and all were confirmed to be p16 positive (172/172, 100%, 95% CI = [97.9%, 100%]). Similarly, 100% of those evaluable for HPV RNA ISH (155/155, 100%, 95% CI = [97.6%, 100%]) were confirmed HPV positive, indicating p16 overexpression driven by transcriptionally active HPV and a PPV of 100% for local p16 testing. Our results validate the suitability of local pathology laboratory p16 testing alone, in populations with a high attributable fraction of OPSCC due to HPV, to screen and enrol low risk HPVOPSCC patients onto de-intensification trials. This obviates the need for upfront more complex and expensive HPV assays and/or central laboratory testing.

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Synchronous reconstruction of esophageal defect and voice with J-flap after laryngopharyngectomy: Indications and outcomes

Yun-Huan Hsieh, Tuan-Jen Fang, Shiang-Fu Huang, Chung-Jan Kang, Chun-Ta Liao, Shao-Yu Hung, Chon-Fok Cheong, Chung-Kan Tsao

Publicatie 25-08-2020


The primary reconstruction goal for patients with laryngopharyngectomy is the restoration of esophagus, whereas voice reconstruction is less readily reconstructed. J-flap is a novel surgical technique designed to reconstruct voice and esophagus synchronously, permitting functional rehabilitation of aerodigestive tract after laryngopharyngectomy. This study aims to present indications, surgical steps, and outcomes of an innovative technique for synchronous reconstruction of the esophagus and voice tube with a free thigh flap (J-flaps). Single-center study from 2011 to 2017 recruiting patients with hypopharyngeal cancer needing laryngopharyngectomy and J-flaps reconstruction. Patient details were analyzed, and surgical outcomes were examined. 20 patients were recruited with an average age of 61. Tumor staging was IIB or above. The average follow-up period was 15 months. 65% of these patients resumed a full diet. The row phonation rate was 75%. The average maximum phonation time was 8.9 s, and the average number of counting in a breath was 14. Most patients achieved a conversational level of speech capacity with a humanoid voice. J-flap can be utilized safely, supporting the social re-integration of these patients with their new voice.

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Novel induction therapy transoral surgery treatment paradigm with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck – Mature clinical and functional outcomes

Trevor G. Hackman, Samip N. Patel, Allison M. Deal, D. Neil Hayes, Bhishamjit S. Chera, Jennifer Paul, Mary Knowles, Dmitriy Usenko, Juneko E. Grilley-Olson, Mark C. Weissler, Jared Weiss

Publicatie 22-08-2020


Induction chemotherapy in head and neck squamous cell carcinoma (HNSCCA) has principally been studied prior to radiation therapy. We evaluated pre-operative induction therapy followed by surgery followed by risk-adapted adjuvant therapy. This report details the mature 5-year survival statistics, clinical and functional outcomes. An IRB-approved single institution prospective phase II clinical trial from October 2012 to November 2016 was conducted for patients with transorally-resectable American Joint Committee on Cancer 7th ed. stage III/IV HNSCCA. Patients were treated once weekly for six weeks with a multi-drug induction regimen of carboplatin, paclitaxel and daily lapatinib followed by transoral surgery and neck dissection. Patients were then stratified based on pathologic response to either observation or adjuvant therapy. Survival statistics and functional patient outcomes were analyzed. Specifically, peri-operative outcomes were analyzed and compared to a matched surgical cohort. 38/40 enrolled patients completed trial therapy. Median hospital stay was 3 days with 9/38 patients receiving a PEG (median 46 days). Median NPO status was 1 day, with a median return to a regular diet in 16 days. Mean patient weight was well preserved from pretreatment to 1 year after surgery (85.1 kg (95% CI 79.6-90.7) vs 83.1 kg (95% CI 77.7-88.6 kg) respectively). Of the 38 patients who completed trial therapy; DSS, PFS and OS were 100%, 97% and 97% respectively with median follow up of 4.9 years (3.33-7.25). Transoral surgery was feasible following this novel induction regimen with excellent peri-operative, functional and longterm survival outcomes.

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Retro-auricular endo assisted selective neck dissection (how I do it)

Prashant Pawar, Sagar Vaishampayan, Dinesh H. Shah, Ameya Pai

Publicatie 23-08-2020


Elective neck dissection (END) is preferred in all treatment naïve patients with invasive oral squamous cell carcinoma (OSCC), including the early stage, node negative cases (T1/T2 N0). Usually the conventional horizontal neck crease incision leads to a faintly visible scar in the neck. However sometimes, the neck scar is hypertrophic and is highly unaesthetic and psychologically distressing to the patient. Retro-auricular hairline approach has been popularized in the Robot assisted neck dissections (RoAND), to avoid easily visible scar in neck crease. We have been using the retro-auricular incision for selective neck dissection in early invasive OSCCs using an assembly of customized retractors as an open approach with only occasional use of endoscopes. This approach to the neck surgery is oncologically safe, reproducible and economical. It is cosmetically superior as the scar of neck dissection is in a less conspicuous area of the face, hidden behind the ear and in the hairline.

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The relevance of surgical margins in clinically early oral squamous cell carcinoma

Mandeep S. Bajwa, David Houghton, Kapil Java, Asterios Triantafyllou, Owais Khattak, Fazilet Bekiroglu, Andrew G. Schache, James S. Brown, James A. McCaul, Simon N. Rogers, Derek Lowe, Jeremy McMahon, Richard J. Shaw

Publicatie 28-07-2020


There is controversy regarding surgical margins in the management of early oral squamous cell carcinoma (OSCC). The main objectives of this study were to assess the: relevance of the margin independent of tumour variables; threshold for a safe margin; relevance of dysplasia at the margin. UK based retrospective multicenter cohort study of patients with previously untreated and clinically early OSCC between 1998 and 2016. All patients had surgery as the primary modality and had surgical staging of the neck. Minimum follow-up was 2 years. Margins were classified as: clear ≥5.0 mm; close 1.0-4.9 mm; involved not cut-through (INC-T) 0.1-0.9 mm; cut-through (C-T) 0 mm. 669 patients were included. After adjusting for tumour variables Cox multivariate regression analysis demonstrated that close margins had similar survival outcomes to clear margins (Hazard Ratio(HR) 0.99 (95%CI 0.50-1.95) for Local Recurrence Free Survival (LRFS); HR 1.08 (95%CI 0.7-1.66) for Disease Free Survival (DFS); HR 0.74 (95%CI 0.44-1.25) for Disease Specific Survival (DSS); HR 0.80 (95%CI 0.58-1.11) for Overall Survival (OS)). C-T margins had significantly worse LRFS (HR 5.01 (95%CI 2.02-12.39)) and DFS (HR 2.58 (95%CI 1.28-5.20)). INC-T margins had significantly worse DFS (HR 1.98 (95% CI 1.01-3.87)). Time dependent receiver operating characteristic curve analysis did not demonstrate a clear margin threshold for LRFS within 24 months (AUC = 0.53 (95%CI 0.41-0.64)). Dysplasia at the margin did not influence LRFS or DFS. Only resection margins <1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment.

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Cancer-associated fibroblast regulation by microRNAs promotes invasion of oral squamous cell carcinoma

Leandro Luongo Matos, Gilberto Mendes Menderico Junior, Thérèse Rachell Theodoro, Fatima Solange Pasini, Marina de Menezes Ishikawa, Andrômeda Aryane Bomtempo Ribeiro, Evandro Sobroza de Mello, Maria Aparecida da Silva Pinhal, Raquel Ajub Moyses, Marco Aurelio Vamondes Kulcsar, Rogério Aparecido Dedivitis, Claudio Roberto Cernea, Luiz Paulo Kowalski

Publicatie 24-07-2020


The objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin α in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.

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A predictive survival model for patients with head and neck squamous cell carcinoma treated with immune check point inhibitors

M. Bonomi, P. Bhateja, M. Issa, B. Klamer, X. Pan, A. Blakaj, V. Karivedu, L. Mousa, D. Mitchell, M Gamez, S. Kang, Nolan B. Seim, M. Old, R. Carrau, J. Rocco, D. Blakaj

Publicatie 24-07-2020


ICIs have expanded treatment options for HNSCC. A minority of the patients respond to these expensive treatments. This is a single institutional retrospective review on 121 unresectable or metastatic HNSCC patients treated with ICIs. We predicted that inflammatory markers available through routine blood work, in addition to clinical characteristics may divide patients into groups more or less likely to respond to these agents. Here we develop and internally validate our nomogram to predict survival in patients treated with ICIs.

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Prognostic value of the tumor volume reduction rate after neoadjuvant chemotherapy in patients with locoregional advanced nasopharyngeal carcinoma

Huiyun Yang, Yuanyuan Liu, Rongjun Zhang, Yaomin Ye, Qiuqiu Chen, Qinghua Qin, Liying Huang, Xi Li, Rui Cai, Huaying Tang, Wei Jiang

Publicatie 18-07-2020


Aim of this study was to evaluate the prognostic value of the tumor volume reduction rate (TVRR) of neoadjuvant chemotherapy (NACT) in patients with locoregional advanced nasopharyngeal carcinoma (NPC). We collected the clinical data of 263 patients with locoregional advanced NPC receiving NACT and subsequent radiotherapy from two hospitals: a training cohort (n = 130) was obtained from one hospital and a validation cohort was obtained the other hospital (n = 133). By follow-up and calculating the TVRR of all patients, the prognostic value of the TVRR was analyzed though a univariate and multivariate Cox regression model. A cut-off point of the TVRR relating to survival was explored by means of the Youden index, and the prognostic value of the TNM stage plus TVRR was measured by creating receiver operating characteristic (ROC) curves. 12.6%, a cut-off point of TVRR, was found to best predict DFS. Patients with a TVRR > 12.6% had better DFS (hazard ratio, 0.160, 95% confidence interval 0.072-0.354; P < 0.001), LRRFS (0.064, 0.013-0.310; 0.001) and DMFS (0.274, 0.106-0.711; 0.008) than patients with a TVRR ≤ 12.6%. The TVRR was a significant independent prognostic factor for OS, DFS, LRRFS and DMFS. Combining the TVRR and TNM stage enhanced the ability to predict DFS and LRRFS. The TVRR of NACT is an independent prognostic factor for patients with locoregional advanced NPC receiving radiotherapy. Adding the TVRR to the original TNM staging system improves the prognostic value for locoregional advanced NPC.

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Evaluation of patient specific care needs during treatment for head and neck cancer

Lara Schorn, Julian Lommen, Christoph Sproll, Gertrud Krüskemper, Jörg Handschel, Julia Nitschke, Benjamin Prokein, Nils-Claudius Gellrich, Henrik Holtmann

Publicatie 17-07-2020


Tumorous diseases of the head and neck region annually occur in more than 550.000 cases worldwide. Little is known about patient specific care needs and potential relationships between non-fulfillment of those following therapeutic and especially surgical treatment of head and neck cancer (HNC). This study aimed to evaluate potential correlations between patient specific care needs, regarding physiological rehabilitation, family/social support, economic needs, and their impact on health-related quality of life (HRQoL). A total of 1359 patients were included in this retrospective analysis. Data derived from the exploratory international multicenter rehabilitation study of the German-Austrian-Swiss Cooperative Group on Tumors of the Maxillofacial Region (DÖSAK), including 43 oral and maxillofacial departments in Germany, Austria, and Switzerland using the Bochum patient questionnaire on rehabilitation and a questionnaire on tumor and treatment related data. Results showed a significant correlation of a patient's social bonds and depression, coping with depression, and anxiety. Patients' needs for speech therapy, physiotherapy or respiratory training were hardly ever met and patients had to compensate for financial losses during hospitalization for acute treatment. In conclusion, this study describes social, physical, and socio-economic care needs. A multidisciplinary approach managing cancer and treatment related side effects is necessary, as well as enhanced awareness of care needs of practitioners during early recovery after surgery.

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A novel surgeon credentialing and quality assurance process using transoral surgery for oropharyngeal cancer in ECOG-ACRIN Cancer Research Group Trial E3311

Robert L. Ferris, Yael Flamand, F. Christopher Holsinger, Gregory S. Weinstein, Harry Quon, Ranee Mehra, Joaquin J. Garcia, Michael L. Hinni, Neil D. Gross, Erich M. Sturgis, Umamaheswar Duvvuri, Eduardo Méndez, John A. Ridge, J. Scott Magnuson, Kerry A. Higgins, Mihir R. Patel, Russel B. Smith, Daniel W. Karakla, Michael E. Kupferman, James P. Malone

Publicatie 18-07-2020


Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA. E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections. 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients. We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.

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Impact of 3\xa0mm margin on risk of recurrence and survival in oral cancer

David Brinkman, Deirdre Callanan, Ross OShea, Hadeel Jawad, Linda Feeley, Patrick Sheahan

Publicatie 14-07-2020


While positive surgical margins in oral squamous cell carcinoma (OSCC) is generally considered an adverse prognosticator, the significance of close (≤5 mm) margins is more debatable, and has not been widely adopted as an indicator for radiotherapy. Retrospective study of 244 patients undergoing primary surgical resection of OSCC. The impact on local control (LC), disease-specific survival (DSS) and overall survival (OS) of margins at 1 mm intervals was studied. 65 patients had involved (<1 mm), 119 close (1-5 mm), and 60 clear (>5 mm) main specimen margins. Involved margins was predictive of DSS (p = 0.04), but not LC (p = 0.20) or OS (p = 0.09). Both the 2 mm and 3 mm margin cut-offs were significantly associated with LC (p = 0.02, and p = 0.01), DSS (p = 0.02, and p = 0.007), and OS (p = 0.03. and p = 0.005). In a 3-tier model, use of 3 mm for demarcation between close and clear yielded good separation between survival curves of clear (≥3 mm), and close (1-<3 mm) or involved (<1 mm). Final margins, determined after incorporation of frozen sections and extra margins taken separately, was significant for LC (p = 0.04), but not for DSS (p = 0.05) or OS (p = 0.17). On multivariate analysis, <3 mm margin, T-classification, nodal status, extranodal spread, and postoperative radiotherapy, were independent predictors of DSS and OS. For LC, only T-classification was significant. A 3 mm main specimen margin is significantly associated with survival in OSCC and may be useful for demarcation between close and clear. Further study is required to determine any impact on survival of radiotherapy for patients with <3 mm margins as sole indicator for radiotherapy.

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Impact of extrinsic tongue muscle invasion on stage migration in AJCC 8th edition staging of oral cavity carcinoma

Emily J. Marchiano, Noah J. Mathis, Emily L. Bellile, Remy Lobo, Mohannad Ibrahim, Joshua D. Smith, Andrew C. Birkeland, Keith A. Casper, Kelly M. Malloy, Paul L. Swiecicki, Francis P. Worden, Michelle L. Mierzwa, J. Chad Brenner, Carol R. Bradford, Chaz L. Stucken, Mark E. Prince, Andrew J. Rosko, Andrew G. Shuman, Jonathan B. McHugh, Matthew E. Spector

Publicatie 14-07-2020


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Assessment of tumour depth in early tongue cancer: Accuracy of MRI and intraoral ultrasound

Rob Noorlag, Thomas J.W. Klein Nulent, Valerie E.J. Delwel, Frank A. Pameijer, Stefan M. Willems, Remco de Bree, Robert J.J. van Es

Publicatie 13-07-2020


Complete resection of tongue cancer is necessary to achieve local control. Unfortunately, deep resection margins are frequently inadequate. To improve deep margin control, accurate knowledge of tumour thickness is pivotal. Magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS) are frequently applied for tumour staging. This study explores the accuracy of these techniques to estimate depth of invasion. The data of patients with a T1-2 tongue cancer that had been treated surgically between 2014 and 2018 were retrospectively analysed. Measurements that had been taken by either MRI or ioUS were compared with those taken during histopathology. A total of 83 patients with tongue cancer had undergone a pre-operative MRI and 107 had been studied through an ioUS. Tumour thickness measured by MRI (r = 0.72) and ioUS (r = 0.78) correlated significantly (p < 0.001) with histopathological depth of invasion (DOI). In tumours with a DOI of 0-10 mm, MRI has a mean absolute difference with histopathology of 3.1 mm (SD 3.2 mm) and ioUS of 1.6 mm (SD 1.3 mm). In tumours with a DOI greater than 10 mm, MRI has a mean absolute difference of 3.5 mm (SD 3.0 mm) and ioUS of 4.7 mm (SD 3.5 mm). Estimation of histopathological DOI in tongue cancers with DOI till 10 mm is very accurate through use of ioUS. ioUS tends to underestimate DOI in tumors exceeding 10 mm DOI. MRI tends to overestimate DOI in both thin and thick tumours. Since ultrasound measurements can be performed during surgery, ioUS could potentially guide the surgeon in the achievement of adequate resection margins.

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Trans oral robotic surgery versus definitive chemoradiotherapy for oropharyngeal cancer: 10-year institutional experience

Giuseppe Meccariello, Giulia Bianchi, Sebastiano Calpona, Elisabetta Parisi, Giovanni Cammaroto, Giannicola Iannella, Rossella Sgarzani, Filippo Montevecchi, Andrea De Vito, Pasquale Capaccio, Stefano Pelucchi, Claudio Vicini

Publicatie 13-07-2020


Trans Oral Robotic Surgery (TORS) is a fascinating new technique that has proved to be a safe and feasible treatment of oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to compare oncological outcomes of OPSCC-patients treated with either TORS (with or without adjuvant therapy) or definitive chemoradiation therapy (CRT). This study involved 129 patients with OPSCC, treated with TORS or definitive CRT at our Department between 2008 and 2018. Clinicopathological characteristics, treatment specifications and oncological outcomes were evaluated retrospectively. Definitive CRT was administered in 69 patients (53,5%), while 60 (46,5%) were surgically treated with TORS alone or in combination with adjuvant therapy. Patients who underwent adjuvant therapy after TORS received a lower dosages of cisplatin and radiation than the CRT group (p < 0.01). There was no statistical difference in 5-year survival rate and in disease free interval between TORS and CRT groups. Albeit 5-year overall survival in the HPV-related tumours was better, the HPV status did not affect the rate of local and regional recurrence. Treatment groups (TORS vs. CRT) were not found affecting survivals on multivariate analysis. Tube feeding dependency rate was low between both groups (1.7% in TORS vs. 4.8% in CRT groups). The modern management of OPSCC must be tailored to each patient. Although the definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of single therapeutic strategy requires an evaluation by a multidisciplinary team.

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Lymph node-to-primary tumor standardized uptake value ratio on PET predicts distant metastasis in nasopharyngeal carcinoma

Tsung-Min Hung, Kang-Hsing Fan, Chung-Jan Kang, Shiang-Fu Huang, Chien-Yu Lin, Albert Tsung-Ying Ho, Hung-Ming Wang, Jason Chia-Hsun Hsieh, Ann-Joy Cheng, Shu-Hang Ng, Joseph Tung-Chieh Chang

Publicatie 12-07-2020


To investigate the prognostic value of the relative maximum standardized uptake value (SUV) ratio between neck lymph node and primary tumor (NTR) measured by pretreatment We retrospectively reviewed patients with non-disseminated NPC who underwent PET scans before radical intensity-modulated radiotherapy (IMRT). Receiver operating characteristic analysis was performed to identify the optimal cut-off value for NTR. The prognostic value of NTR for distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier method for survival analyses and Cox regression for multivariable analysis. Among the 437 eligible patients, the median follow-up time was 62.9 (range, 2.1-113.0) months. Patients with high NTR (NTR > 0.9181) experienced significantly worse DMFS (5-year 80.5% vs. 91.6%, P < 0.001). In the subgroup analysis, we found that patients with high NTR had significantly lower DMFS in T1-2 category (5-year 86.1% vs. 98.1%, P = 0.002), T3-4 category (5-year 71.5% vs. 86.2%, P = 0.010), N2-3 category (5-year 75.3% vs. 86.2%, P = 0.048), and stage IVA-B (5-year 69.8% vs. 85.4%, P = 0.012). Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (HR 2.20, 95% CI 1.20-4.03, P = 0.011). Pretreatment NTR is an easily accessible but potential prognosticator for DMFS in NPC patients treated by IMRT, which may help in providing more personalized treatment or designing future clinical trials.

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The role of concomitant chemoradiotherapy in AJCC 7th edition T1-2N1 oropharyngeal carcinoma in the human papillomavirus era

Diana J. Lu, Michael Luu, Anthony T. Nguyen, Stephen L. Shiao, Kevin Scher, Alain Mita, Eric Anderson, Jon Mallen-St. Clair, Allen S. Ho, Zachary S. Zumsteg

Publicatie 11-07-2020


Radiotherapy (RT) without chemotherapy is considered a standard of care for the management of American Joint Committee on Cancer (AJCC) 7th edition (7E) T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC). Recent data suggests concurrent chemoradiation (CCRT) may benefit these patients but did not include human papillomavirus (HPV) status. Given the radiosensitivity differences between HPV-positive versus HPV-negative OPSCC, the effect of chemotherapy may differ in these patients. We analyzed patients in the National Cancer Database diagnosed between 2010 and 2015 with AJCC 7E stage cT1-2N1M0 OPSCC and known HPV status undergoing definitive RT or CCRT. Overall, 1964 patients were included, including 1297 (66%) HPV-positive and 667 (34%) HPV-negative patients. 66% received CCRT and 34% received RT alone. In multivariate analysis, CCRT was associated with improved survival compared with RT alone (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.57-0.87; P = 0.001). In propensity score-matched cohorts, 4-year overall survival was 87.4% vs 78.4% in HPV-positive patients receiving CCRT and RT alone, respectively (P = 0.002), and 65.5% vs 58.9% in HPV-negative patients, respectively (P = 0.2). There was no evidence that HPV-positivity diminished the association between CCRT and longer survival (HR, 0.57; 95% CI, 0.42-0.81) versus what was observed in HPV-negative patients (HR, 0.86; 95% CI, 0.64-1.16) (interaction P = 0.06). CCRT is associated with improved survival in AJCC 7E T1-2N1 OPSCC. Despite the radiosensitivity of HPV-positive OPSCC, the association of CCRT with improved survival for T1-2N1 HPV-positive OPSCC was at least as strong, if not stronger, than what was observed in HPV-negative patients.

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Cost-effectiveness of routine calcitonin screening and fine-needle aspiration biopsy in preoperative diagnosis of medullary thyroid Cancer in the United States

Zaid Al-Qurayshi, Emad Kandil, Gregory W Randolph

Publicatie 12-07-2020


examine the cost-effectiveness of routine Calcitonin (Ctn) screening test in the United States. Markov chain model was developed that compares fine-needle aspiration biopsy (FNAB) with Ctn screening vs. FNAB-only in the evaluation of a thyroid nodule with non-highly suspicious findings. Follow-up time was set as 10 years. Costs and probabilities values were obtained from literature, and National Cancer Database. Cost data is expressed in U.S$ and effectiveness is expressed in Quality-adjusted-life-year (QALY). Incremental cost-effectiveness ratio (ICER) was calculated comparing both study arms. Routine Ctn screening was cost-effective compared to FNAB-only in all tested categories except when cutoff value of 10 pg/ml was applied. Among the tested categories, the application of universal routine Ctn screening with Ctn value > 50 pg/ml considered a positive test produced the most cost-saving scenario. The final accrued cost at the end of 10 years in the FNAB-only arm was $4238.93 with a final effectiveness of 8.717 QALY. While the final cost in the FNAB-with routine Ctn screening was $4345.04 with a final effectiveness of 8.722 QALY. ICER of routine Ctn screening compared to FNAB-only was $23278.61/QALY ( Pubmed PDF Web


Clinical-pathological prognostic factors and treatment failure patterns in T1-2 high-grade parotid gland cancer

Young Min Park, Sun Och Yoon, Yoon Woo Koh, Se-Heon Kim, Jae-Yol Lim, Eun Chang Choi

Publicatie 07-07-2020


The purpose of this study was to evaluate the treatment outcomes of patients with T1-2, high-grade parotid cancer, and to analyze the prognostic factors and treatment failure patterns. Of the 101 patients who were diagnosed with high-grade parotid cancer from March 2003 to December 2018, a total of 39 males and 23 females who had T1-2 tumor were enrolled in this study. The average follow-up period of patients in this study was 63.9 months. The 5-year overall survival rate was 73.0%, and the 5-year disease-free survival rate was 57.6%. Thirty-nine patients underwent less-than-total parotidectomies, and the remaining 23 patients underwent total parotidectomies. After surgery, 50 patients received adjuvant treatment. During the study, 25 recurrences were documented, including nine local recurrences and 16 distant metastases. The average time period between the end of initial treatment and disease relapse was 17.0 months. A total of 16 patients succumbed to disease progression. Multivariate Cox proportional regression analysis showed that lymphovascular invasion (LVI) was an independent prognostic factor affecting disease recurrence and patient deaths. Among various factors, LVI and lymph node (LN) metastasis showed statistically significant correlations with distant metastasis. Although we achieved favorable therapeutic results using standard treatments in selected patients, T1-2 high-grade parotid cancers generally have poor prognosis. Distant metastases that occur during follow-up are a major factor in treatment failure and LVI and LN metastasis are significantly associated with distant metastasis.

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State Medicaid expansion status, insurance coverage and stage at diagnosis in head and neck cancer patients

Nosayaba Osazuwa-Peters, Justin M. Barnes, Uchechukwu Megwalu, Eric Adjei Boakye, Kenton J. Johnston, Matthew E. Gaubatz, Kimberly J. Johnson, Neelima Panth, Rosh K.V. Sethi, Mark A. Varvares

Publicatie 07-07-2020


Only one in three head and neck cancer (HNC) patients present with early-stage disease. We aimed to quantify associations between state Medicaid expansions and changes in insurance coverage rates and stage at diagnosis of HNC. Using a quasi-experimental difference-in-differences (DID) approach and data from 26,330 cases included in the Surveillance, Epidemiology, and End Results program (2011-2015), we retrospectively examined changes in insurance coverage and stage at diagnosis of adult HNC in states that expanded Medicaid (EXP) versus those that did not (NEXP). There was a significant increase in Medicaid coverage in EXP (+1.6 percentage point (PP) versus) vs. NEXP (-1.8 PP) states (3.36 PP, 95% CI = 1.32, 5.41; p = 0.001), and this increase was mostly among residents of low income and education counties. We also observed a reduction in uninsured rates among HNC patients in low income counties (-4.17 PP, 95% CI = -6.84, -1.51; p = 0.002). Overall, early stage diagnosis rates were 28.3% (EXP) vs. 26.7% (NEXP), with significant increases in early stage diagnosis post-Medicaid expansion among young adults, 18-34 years (17.2 PP, 95% CI - 1.34 to 33.1, p = 0.034), females (7.54 PP, 95% CI = 2.00 to 13.10, p = 0.008), unmarried patients (3.83 PP, 95% CI = 0.30-7.35, p = 0.033), and patients with lip cancer (13.5 PP, 95% CI = 2.67-24.3, p = 0.015). Medicaid expansion is associated with improved insurance coverage rates for HNC patients, particularly those with low income, and increases in early stage diagnoses for young adults and women.

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“Sushi roll” technique for precise total tongue functional reconstruction using a pre-sutured femoral anterolateral myocutaneous flap

Xi Zhou, Zhi-Jing He, Yu-Xiong Su, Sheng Zhang, Zhao Jian Gong, Han Jiang Wu

Publicatie 06-07-2020


Reconstruction of the total tongue after cancer resection remains one of the challenges in head and neck surgery. Inadequate reconstruction after subtotal or total glossectomy defects leads to poor quality of life. The aim of this study was to explore an economical, practical and effective flap design for functional tongue reconstruction. Sixty patients were randomly divided into two groups, namely, a "Sushi roll" technique group (30 patients) and a conventional surgery group (30 patients). Then, the patients underwent total or subtotal tongue reconstruction. Swallowing function, speech intelligibility, cosmetic results, and quality of life were assessed with the appropriate scales. Outcomes were analysed, and a p-value <0.05 was considered significant. The perioperative recovery of the "Sushi roll" group was superior to that of the conventional group. Relative to patients in the conventional group, patients in the "Sushi roll" group showed significantly improved speech intelligibility (p = 0.025), cosmetic results (p < 0.001) and swallowing function (p < 0.001). The innovative "Sushi roll" anterolateral thigh myocutaneous flap approach for total tongue reconstruction creates a free neotongue tip with adequate volume and protuberance and causes minimal damage to the donor site, producing acceptable swallowing function and speech intelligibility.

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The incidence of squamous cell carcinoma of the oral tongue is rising in young non-smoking women: An international multi-institutional analysis

Laveniya Satgunaseelan, Benjamin M. Allanson, Rebecca Asher, Rithvik Reddy, Hubert T.H. Low, Michael Veness, N. Gopal Iyer, Robert I. Smee, Carsten E. Palme, Ruta Gupta, Jonathan R. Clark

Publicatie 06-07-2020


Increasing evidence is accumulating for an alarming rising incidence of oral tongue SCC in a younger cohort, particularly in developed countries. The aim of this study is to analyse the change in incidence of OSCC in patients under the age of 45 in developed nations in the Asia-Pacific region. Population data was extracted from the Australian Cancer Incidence and Mortality 2017 database and National Registry of Diseases Office, Singapore to allow calculation of the incidence in the Australian and Singaporean populations. This was compared to multi-institutional data from four tertiary Australian institutions. The inclusion criteria were as follows: a) diagnosis of primary SCC of the mobile tongue; b) treatment with curative intent; c) complete histopathologic data; d) complete adjuvant treatment data; e) follow up data. Analysis of ACIM data demonstrated that there was a significant increase in the incidence of tongue SCC in those under the age of 45 in the Australian and Singaporean populations (p < 0.001). When analysed for gender, the incidence of tongue SCC increased at a significantly higher rate in females than males (p < 0.001). Similarly, in the multi-institutional analysis including 1814 patients, the number of females under the age of 45 with tongue SCC significantly increased over time (p < 0.001), with the proportion of smokers in this cohort decreasing over time. The incidence of tongue SCC is rising in young females in developed nations in the Asia Pacific region, in keeping with observed epidemiological trends worldwide.

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Radiomic analysis identifies tumor subtypes associated with distinct molecular and microenvironmental factors in head and neck squamous cell carcinoma

Evangelia Katsoulakis, Yao Yu, Aditya P. Apte, Jonathan E. Leeman, Nora Katabi, Luc Morris, Joseph O. Deasy, Timothy A. Chan, Nancy Y. Lee, Nadeem Riaz, Vaios Hatzoglou, Jung Hun Oh

Publicatie 04-07-2020


To identify whether radiomic features from pre-treatment computed tomography (CT) scans can predict molecular differences between head and neck squamous cell carcinoma (HNSCC) using The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 77 patients from the TCIA with HNSCC had imaging suitable for analysis. Radiomic features were extracted and unsupervised consensus clustering was performed to identify subtypes. Genomic data was extracted from the matched patients in the TCGA database. We explored relationships between radiomic features and molecular profiles of tumors, including the tumor immune microenvironment. A machine learning method was used to build a model predictive of CD8 + T-cells. An independent cohort of 83 HNSCC patients was used to validate the radiomic clusters. We initially extracted 104 two-dimensional radiomic features, and after feature stability tests and removal of volume dependent features, reduced this to 67 features for subsequent analysis. Consensus clustering based on these features resulted in two distinct clusters. The radiomic clusters differed by primary tumor subsite (p = 0.0096), HPV status (p = 0.0127), methylation-based clustering results (p = 0.0025), and tumor immune microenvironment. A random forest model using radiomic features predicted CD8 + T-cells independent of HPV status with R Radiomic analysis can identify biologic features of tumors such as HPV status and T-cell infiltration and may be able to provide other information in the near future to help with patient stratification.

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Transoral thyroidectomy (TOETVA): Complications, surgical time and learning curve

Renan Bezerra Lira, Andressa Teruya Ramos, Ricardo Miguel Ribeiro Nogueira, Genival Barbosa de Carvalho, Jonathon O. Russell, Ralph P. Tufano, Luiz Paulo Kowalski

Publicatie 04-07-2020


Since 2018, transoral endoscopic thyroidectomy vestibular approach (TOETVA) has emerged as a true scarless thyroid surgery. In this study, we explore early outcomes and learning curve of this new approach. A retrospective cohort including conventional thyroidectomies and TOETVAs performed in a cancer center was designed. Learning curve and early surgical outcomes of TOETVA were assessed and compared to conventional thyroidectomy. A total of 56 TOETVAs and 745 conventional thyroid procedures were included. In the TOETVA group, we had a 14.4% total complication rate with no permanent vocal cord paresis or hypocalcemia. The mean surgical time dropped from 167 to 117 min (p = 0.0001) after the 15 first cases. Comparing to conventional procedures, we didn't find any significant difference in complications rate. Operative time was longer in the TOETVA group. In this study, TOETVA was safe and feasible, with a learning curve of 15 cases.

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Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension

John R. de Almeida, Tra Truong, Nazir Mohemmed Khan, Jie Susie Su, Jonathan Irish, Ralph Gilbert, David Goldstein, Shao Hui Huang, Brian OSullivan, Ali Hosni, Andrew Hope, John Waldron, Aaron R. Hansen, Anna Spreafico, Lillian L. Siu, Bayardo Perez-Ordonez, Wei Xu, Ilan Weinreb

Publicatie 03-07-2020


To evaluate adjuvant chemoradiotherapy (CRT) for patients with oral cavity squamous cell carcinoma (OSCC) with minor or major extranodal extension (ENE). Surgically resected OSCC with pathologically involved lymph node(s) (pN+) between 2006 and 2017. Sections of pN+ were re-reviewed and classified as no, minor (≤2 mm), or major (>2 mm) ENE. Patterns of failure and survival were compared between the groups and stratified by adjuvant treatment. Multivariable (MVA) analysis assessed the value of adjuvant treatment for minor and major ENE. Total of 384 patients, 62 had minor and 114 had major ENE. Adjuvant CRT was delivered in 32(15%), 21(34%), and 45(39%) of patients with no, minor and major ENE, respectively. Patients with minor ENE had similar 5-year loco-regional control (LRC) and distant control (DC) but lower disease-free survival (DFS) (38% vs. 51%, p = 0·02) compared to patients with no ENE, while patients with major ENE had marginally lower LRC (59% vs 74%, p = 0·07), lower DC (58% vs 82%,p = 0·005) and DFS (13% vs. 38%, p=·001) compared to those with minor. On MVA, adjuvant chemotherapy was associated with improved DFS for major ENE (adjusted HR = 0·49; 95% CI 0·29-0·85, p = 0·01) but not for minor ENE after adjusting for age, ECOG status, T-, N-category, margin status, and radiotherapy. Adjuvant chemoradiotherapy improves outcomes in patients with major ENE, but the benefit is unclear in patients with minor ENE. Future trials should focus on intensification of treatment for patients with major ENE and alternative adjuvant strategies for patients with minor ENE.

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Development of a self-constrained 3D DenseNet model in automatic detection and segmentation of nasopharyngeal carcinoma using magnetic resonance images

Liangru Ke, Yishu Deng, Weixiong Xia, Mengyun Qiang, Xi Chen, Kuiyuan Liu, Bingzhong Jing, Caisheng He, Chuanmiao Xie, Xiang Guo, Xing Lv, Chaofeng Li

Publicatie 03-07-2020


We aimed to develop a dual-task model to detect and segment nasopharyngeal carcinoma (NPC) automatically in magnetic resource images (MRI) based on deep learning method, since the differential diagnosis of NPC and atypical benign hyperplasia was difficult and the radiotherapy target contouring of NPC was labor-intensive. A self-constrained 3D DenseNet (SC-DenseNet) architecture was improved using separated training and validation sets. A total of 4100 individuals were finally enrolled and split into the training, validation and test sets at a proximate ratio of 8:1:1 using simple randomization. The diagnostic metrics of the established model against experienced radiologists was compared in the test set. The dice similarity coefficient (DSC) of manual and model-defined tumor region was used to evaluate the efficacy of segmentation. Totally, 3142 nasopharyngeal carcinoma (NPC) and 958 benign hyperplasia were included. The SC-DenseNet model showed encouraging performance in detecting NPC, attained a higher overall accuracy, sensitivity and specificity than those of the experienced radiologists (97.77% vs 95.87%, 99.68% vs 99.24% and 91.67% vs 85.21%, respectively). Moreover, the model also exhibited promising performance in automatic segmentation of tumor region in NPC, with an average DSC at 0.77 ± 0.07 in the test set. The SC-DenseNet model showed competence in automatic detection and segmentation of NPC in MRI, indicating the promising application value as an assistant tool in clinical practice, especially in screening project.

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Molecular margins in head and neck cancer: Current techniques and future directions

Katelyn O. Stepan, Michael M. Li, Stephen Y. Kang, Sidharth V. Puram

Publicatie 24-07-2020


Complete tumor extirpation with clear surgical margins remains a central tenet of oncologic head and neck surgery. Rates of locoregional recurrence and survival are both significantly worse when clear margins are unable to be obtained. Current clinical practice relies on the use of frozen sections intra-operatively, followed by traditional histopathologic analysis post-operatively to assess the surgical margin. However, with improved understanding of tumor biology and advances in technology, new techniques have emerged to analyze margins at a molecular level. Such molecular margin analysis interrogates tissue for genetic, epigenetic, or proteomic changes that may belie tumor presence or aggressive features not captured by standard histopathologic techniques. Intra-operatively, this information may be used to guide resection, while post-operatively, it may help to stratify patients for adjuvant treatment. In this review, we summarize the current state of molecular margin analysis and describe directions for future research.

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Use of artificial intelligence in diagnosis of head and neck precancerous and cancerous lesions: A systematic review

H. Mahmood, M. Shaban, B.I. Indave, A.R. Santos-Silva, N. Rajpoot, S.A. Khurram

Publicatie 17-07-2020


This systematic review analyses and describes the application and diagnostic accuracy of Artificial Intelligence (AI) methods used for detection and grading of potentially malignant (pre-cancerous) and cancerous head and neck lesions using whole slide images (WSI) of human tissue slides. Electronic databases MEDLINE via OVID, Scopus and Web of Science were searched between October 2009 - April 2020. Tailored search-strings were developed using database-specific terms. Studies were selected using a strict inclusion criterion following PRISMA Guidelines. Risk of bias assessment was conducted using a tailored QUADAS-2 tool. Out of 315 records, 11 fulfilled the inclusion criteria. AI-based methods were employed for analysis of specific histological features for oral epithelial dysplasia (n = 1), oral submucous fibrosis (n = 5), oral squamous cell carcinoma (n = 4) and oropharyngeal squamous cell carcinoma (n = 1). A combination of heuristics, supervised and unsupervised learning methods were employed, including more than 10 different classification and segmentation techniques. Most studies used uni-centric datasets (range 40-270 images) comprising small sub-images within WSI with accuracy between 79 and 100%. This review provides early evidence to support the potential application of supervised machine learning methods as a diagnostic aid for some oral potentially malignant and malignant lesions; however, there is a paucity of evidence using AI for diagnosis of other head and neck pathologies. Overall, the quality of evidence is low, with most studies showing a high risk of bias which is likely to have overestimated accuracy rates. This review highlights the need for development of state-of-the-art deep learning techniques in future head and neck research.

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Past, present and future of proton therapy for head and neck cancer

Xingzhe Li, Anna Lee, Marc A. Cohen, Eric J. Sherman, Nancy Y. Lee

Publicatie 11-07-2020


Proton therapy has recently gained substantial momentum worldwide due to improved accessibility to the technology and sustained interests in its advantage of better tissue sparing compared to traditional photon radiation. Proton therapy in head and neck cancer has a unique advantage given the complex anatomy and proximity of targets to vital organs. As head and neck cancer patients are living longer due to epidemiological shifts and advances in treatment options, long-term toxicity from radiation treatment has become a major concern that may be better mitigated by proton therapy. With increased utilization of proton therapy, new proton centers breaking ground, and as excitement about the technology continue to increase, we aim to comprehensively review the evidence of proton therapy in major subsites within the head and neck, hoping to facilitate a greater understanding of the full risks and benefits of proton therapy for head and neck cancer.

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A case report of a patient with first phenotype of papillary thyroid carcinoma and heterochronous multiprimary tumor harboring germline MUTYH Arg19*/Gly286Glu mutations

Mingbo 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.

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Panitumumab as an effective maintenance treatment in metastatic squamous cell carcinoma of the head and neck

Ruth Gabriela Herrera Gómez, Khalil Saleh, Lamia Mayache, Mariana Iacob, Neus Baste, Caroline Even

Publicatie 06-09-2020


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Duplication of the internal jugular vein – A rare anatomical variation

Sandeep Bhoriwal, Jyoti Sharma, Kunal Dhall, Amitabha Mandal, Madiwalesh Chhebbi, T.S.H.V. Surya

Publicatie 06-09-2020


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Early onset of head and neck squamous-cell carcinoma and fatal toxicity with concurrent chemoradiotherapy in a patient compound heterozygote for FANCA gene

Marie Martin, Brieuc Sautois

Publicatie 06-09-2020


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Tumour spillage of the pleomorphic adenoma of the parotid gland: A proposal for intraoperative measures

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.

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Unique role of HPV16 in predicting oropharyngeal cancer risk more than other oncogenic oral HPV infections

Carole Fakhry, Nicholas Fung, Sakshi R. Tewari, Gypsyamber DSouza

Publicatie 03-09-2020


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A relook at how we assess tumor margins: Is it ‘TIME’ for new criteria?

Yash P. Merchant, Anand Subash, Sameep Shetty, Abhijith George, Akshay Kudpaje, Vishal U.S. Rao

Publicatie 31-08-2020


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Classification of three prognostically different groups of Head and Neck Cancer patients based on their metabolic response to induction chemotherapy (IC-1)

A. Singh, C.A. Singh, K. Sikka

Publicatie 26-08-2020


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Insights on betel-quid and coca chewing

Prashanth Panta

Publicatie 25-08-2020


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ALG8-RET: A novel RET rearrangement in a patient with malignant melanoma of the palatal mucosal

Dongliang Wei, Dongsheng Chen, Lijian Li, Jing Tian, Guoxin Ren

Publicatie 23-08-2020


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Macro-follicular variant of papillary carcinoma of thyroid with mediastinal lymphadenopathy – A rare histology and surgical challenge

Itisha Chaudhary, Mahesh Sultania, Pavithra Ayyanar, Pritinanda Mishra, Amit Kumar Adhya, Dillip Kumar Muduly, Madhabananda Kar

Publicatie 10-08-2020


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Recurrent Aggressive Primary Mandibular Paraganglioma: Deciphering its Origin

B. Vigneshwaran, Swagatika Samal, Mukund Namdev Sable, Amit Kumar Adhya, DillipKumar Muduly, Madhabanada Kar, Boyina Kiran Kumar, Mahesh Sultania

Publicatie 29-07-2020


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The dangers of delaying treatment in oral cancer: A seventeenth-century perspective

Hannah Newton, Amie Bolissian, Dáire Shanahan

Publicatie 28-07-2020


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Clinical comments on prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma (OSCC)

Rama Jayaraj, Sameep Shetty, Chellan Kumaraswamy, S. Raghul, K.M Gothandam, Greg Raymond, Ram M. Ravishankar, Peter Shaw

Publicatie 21-07-2020


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Inverted papilloma of the Oropharynx: A case of extrasinonasal inverted papilloma with an EGFR mutation

Eiichi Sasaki, Katsuhiro Masago, Shiro Fujita, Michi Sawabe, Nobuhiro Hanai, Waki Hosoda

Publicatie 16-07-2020


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Complete response with talimogene laherparepvec in recurrent melanoma of the ear: A case report

Ashley C. Hsu, Niels C. Kokot, Burton L. Eisenberg, Jacob S. Thomas

Publicatie 16-07-2020


The current standard of care for cutaneous melanoma of the ear is surgical excision. This approach may result in unfavorable functional and cosmetic outcomes. We report here a case of recurrent melanoma of the ear that achieved complete response with talimogene laherparepvec treatment after the patient declined surgical resection.

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A case of lip squamous cell carcinoma with a familial history of Xeroderma pigmentosum

Rami Dartaha, Amira Yasmine Benmelouka, Afnan W.M. Jobran

Publicatie 14-07-2020


Xeroderma pigmentosum is an orphan hereditary photosensitive human disorder that is recognized by the development of skin lesions in sun-exposed regions of the body due to severe photosensitivity. Patients with this condition have an abnormal DNA repair process due to a genetic mutation. Xeroderma pigmentosum is considered as a risk factor of cancer since the affected population may develop various cutaneous cancers including both melanoma and non-melanoma cutaneous malignancies even at a younger age than the general population. This risk concerns also asymptomatic heterozygote individuals. Here, we present a case of 46 years old man with a familial history of Xeroderma pigmentosum who developed a microscopically confirmed squamous cell carcinoma of the lip.

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Lymph node ratio in oral cavity cancer and its impact on mortality and disease recurrence

Pallvi Kaul, Achyuth Panuganti, Abhinav Thaduri, Mahendra Pal Singh, Pankaj Kumar Garg

Publicatie 15-07-2020


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Depth of invasion applied to oropharynx does not improve prognosis discrimination according to AJCC stage groups for oral cancer

Leandro Luongo Matos, Renan Aguera Pinheiro, Luiz Paulo Kowalski

Publicatie 14-07-2020


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AKAP13-NTRK3: A novel NTRK3 oncogenic fusion variant in a patient with melanoma

Dongliang Wei, Chuang Qi, Yuan Wu, Xing Zhang, Guoxin Ren

Publicatie 14-07-2020


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The impact of the COVID-19 pandemic on head and neck cancer patients

Gaili Chen, Qiuji Wu, Huangang Jiang, Yahua Zhong

Publicatie 15-07-2020


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Osteonecrosis of the jaw in a metastatic lung cancer patient with bone metastases undergoing pembrolizumab\xa0+\xa0denosumab combination therapy: Case report and literature review

Yoshinari Myoken, Yoshinori Fujita, Kazuma Kawamoto, Shigeaki Toratani

Publicatie 02-07-2020


The rare adverse drug reaction MRONJ (medication-related osteonecrosis of the jaw) can be induced by treatment with antiresorptive, antiangiogenic, or immunomodulating agents. Immune checkpoint inhibitors (ICIs; e.g., pembrolizumab) are the standard care for advanced or metastatic cancer patients. Denosumab directed against receptor activator of NF-kB ligand (RANKL) is approved for preventing skeletal-related events (SREs) in cancer patients with bone metastases. The combination therapy of ICIs + denosumab has shown promising efficacy and no unexpected safety issues in metastatic melanoma and lung cancer patients with bone metastases. We present a rare case of advanced mandibular osteonecrosis in an adult female with metastatic lung cancer and bone metastases who received concomitant pembrolizumab + denosumab.

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Cervical soft tissue deposits: An under-evaluated entity

B.M. Joshna, Ritvi K. Bagadia, Abhijith George, Anand Subash, Shalini Thakur, Vishal U.S. Rao

Publicatie 28-06-2020


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Psychological issues in head and neck cancer survivors: Need for addressal in rehabilitation

Ankita Kar, Asheem M R, Udayan Bhaumik, Vishal U.S. Rao

Publicatie 23-06-2020


Rehabilitation in head and neck cancer (HNC) survivors is a lengthy process, based on multiple correlates and is associated with multiple challenges. The authors have tried to depict the psychological issues associated with the rehabilitation of these patients. Problems and discussion: HNC survivors have to undergo a traumatic and stressful process on the path to recovery. They may face are disfigurement, body image disturbances and limitation of activities which increases likelihood of anxiety and depression. The psychological state in these patients affect treatment adherence, successful rehabilitation, morbidity and overall survival through a multifactorial mechanism. CONCLUSIONS: There is need for multidisciplinary care in rehabilitation of head and neck cancer patients to help them cope with stress. Inclusion of a psychiatrist in the rehabilitation team is likely to lead to early evaluation and addressal of mental health concerns and improve quality of life and chances of survival.

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Reply to letter to editor – Dr Arya’s response to “Imaging in oral cancers: A comprehensive review”

Abhishek Mahajan, Ankita Ahuja, Nilesh Sable, Hilda E. Stambuk

Publicatie 15-06-2020


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Adequate thyroidectomy in laryngectomy

Bipin T. Varghese, Deepak Janardhan, Elizabeth Mathew Iype

Publicatie 03-06-2020


Optimal resection of the involved portion of the thyroid gland is decisive in long term functional and oncologic results of a Laryngectomy. Regardless of the setting and techniques adopted in performing the laryngeal surgery, we propose a concept of adequate removal of the infiltrated thyroid glandular tissue based on the current status of available literature and our own published experience of managing the thyroid gland in laryngectomies.

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MRONJ and ORNJ: When a single letter leads to substantial differences

Valentina Terenzi, Marco Della Monaca, Ingrid Raponi, Andrea Battisti, Paolo Priore, Giorgio Barbera, Umberto Romeo, Antonella Polimeni, Valentino Valentini

Publicatie 02-06-2020


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Grade as prognostic variable in early tongue cancer patients: Are we getting off the track?

Abhinav Thaduri, Amit Sehrawat, Dharma Ram Poonia, Mahendra Pal Singh, Nilotpal Chowdhury

Publicatie 31-05-2020


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Stage pN3a in oral cancer: A redundant entity?

Narayana Subramaniam, Jonathan Robert Clark, David Goldstein, John de Almeida, Ali Hosni Ali Abdalaty, Deepak Balasubramanian, Krishnakumar Thankappan, Subramania Iyer, Martin Batstone, N. Gopal Iyer, Robert I. Smee, Naveen Hedne Chandrasekhar, Vijay Pillai, Vivek Shetty, Vidyabhushan Rangappa, Michael Veness, Tsu-Hui (Hubert) Low

Publicatie 30-05-2020


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Surgical sequence of neck dissection and primary tumor excision could impact the locoregional recurrence rates in oral squamous cell carcinoma

K. Devaraja

Publicatie 26-05-2020


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