Oral Oncology 2024-09-18

Comment on “The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-) radiotherapy”

Gayathri Rengasamy, Vishnu Priya Veeraraghavan

Publication date 18-09-2024


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Commentary on “Impact of high-risk EBV strains on nasopharyngeal carcinoma gene expression.”

Siva Dharshini Rajathirajan

Publication date 16-09-2024


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Commentary on “Predictive value of CXCL1+_FAP+ phenotype in CAFs for distant metastasis and its correlation with PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma patients”

Siva Dharshini Rajathirajan

Publication date 16-09-2024


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Variant of internal jugular vein reconstruction in bilateral radical neck dissection

Grace Paka Lubamba, Yufei Hua, Mingzhe Bao, Gaowei Zhang, Wei Liu, Diya Wang, Guile Zhao, Guiquan Zhu, Longjiang Li, Ning Gao, Chunjie Li

Publication date 14-09-2024


The internal jugular vein (IJV) plays a major role in collecting venous blood from the cranium, face, and neck. Preserving or reconstructing at least one IJV during bilateral radical neck dissection (RND) allows preventing severe complications. The aim of this report was to present a variant of IJV reconstruction in bilateral radical neck dissection. A 55-year-old male complained for a gingival mass for about 2 months, which was approximately 4 × 2 cm in size with a surface ulceration, located in the anterior mandibular area. There were bilateral cervical adenopathy. The computed tomography (CT) scan revealed mandibular bone destruction with surrounding soft tissue masse, multiple enlarged lymph nodes around bilateral submandibular space and bilateral carotid sheath, with obvious necrosis in the center. The preoperative diagnosis was mandibular gingiva squamous cell carcinoma (SCC), staged T4aN2bM0. Under general anesthesia, the patient underwent bilateral RND with sacrifice of right IJV and reconstruction of left IJV by anastomosis of IJV to the ipsilateral EJV using the common facial vein as a communicating way, followed by an expanded resection of mandibular gingiva SCC via marginal mandibulectomy, left anterolateral thigh (ALT) free flap reconstruction of the resulting defects, and tracheotomy. The patient's post-operative course was uneventfully. In our case report, the immediate IJV reconstruction by the W method was performed without compromising oncologic principles and was found feasible, safe and effective to prevent the occurrence of severe postoperative complications related to bilateral RND with sacrifice of both IJV.

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Authors reply to the comment on: Association of sarcopenia with oncologic outcomes of primary treatment among patients with oral cavity cancer: A systematic review and meta-analysis

Jeffrey P. Graves, Ghazal S. Daher, Megan M.J. Bauman, Eric J. Moore, Kendall K. Tasche, Daniel L. Price, Kathryn M. Van Abel

Publication date 12-09-2024


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Personalized intraoral devices in the era of high-technology head and neck radiotherapy: A resource to be explored

Breno Amaral Rocha, Mateus Costa Lima, Lucianne Maia Costa, Mayra Mendes Soares Teixeira, Angel da Silva Martinez, Carlos Antônio Lopes Junior, Martinho Campolina Rebello Horta

Publication date 11-09-2024


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Letter to Editor regarding “Circulating tumor tissue modified viral (TTMV)-HPV DNA in Recurrent, metastatic HPV-driven oropharyngeal cancer”

Sathish Sankar

Publication date 09-09-2024


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MRI-based deep learning and radiomics for occult cervical lymph node metastasis (OCLNM) prediction

Sesuraj Balasamy, Jayalakshmi Somasundaram, Ashok K. Sundramoorthy

Publication date 09-09-2024


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Commentary on “Tumor Habitat-Based MRI features assessing early response in locally advanced nasopharyngeal carcinoma”

T. Prithviraj

Publication date 09-09-2024


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Early return to work is possible after transoral robotic surgery (TORS) in carefully selected patients with oropharyngeal squamous cell carcinoma

Lorne Green, Lachlan McDowell, Fiona Ip, Mario Tapia, Meiling Zhou, Michael T. Fahey, Benjamin Dixon, Matthew Magarey

Publication date 18-09-2024


The aims of this study were to investigate the rate and time to return to work (RTW) after transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) and to explore the impact of disease or work-related factors leading to variations in RTW outcomes. Cross-sectional survey of disease, socioeconomic, work-related and health-related quality of life (HR-QOL). Qualitative analysis of responses for facilitators and barriers to RTW. A total of 47 participants employed at diagnosis were included in the study, with an average age 56 years. Median survey time 3.2 years. 22 participants underwent TORS only with 25 undergoing TORS with adjuvant therapy. 93.6 % had stage 1 disease. 95.7 % of participants RTW after TORS with a mean time of 13.6 weeks. Patients returned earlier after TORS alone compared to those requiring adjuvant treatment (10 weeks vs. 17 weeks; p = 0.13) Overall high HR-QOL metrics for all patients, with those undergoing adjuvant having significantly poorer outcomes for the dry mouth/sticky saliva (9.1 vs 41.3, p=<0.001) items.
Qualitative analysis of free text responses showed facilitators and barriers to RTW fell under four main categories: physical, phycological/emotional, financial and workplace. High rate of RTW amongst patients after TORS, which is the highest reported amongst head and neck cancer literature to date. Participants returned earlier after surgery only compared to adjuvant treatment, but both groups reported high HR-QOL metrics. Physical effects of treatment, including fatigue and oral dysfunction were some of the main barriers to RTW; whereas flexible working arrangements and support from employer/colleagues were major facilitators.

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L48H37, a curcumin analog, suppresses matrix metalloproteinase-9 expression and activity to hamper nasopharyngeal cancer cell migration

Yen-Ting Lu, Chiao-Wen Lin, Shih-Chi Su, Yu-Ting Ho, Fang-Ling Yeh, Chung-Han Hsin, Shun-Fa Yang

Publication date 17-09-2024


Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.

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Return to work and self-reported swallowing following transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma: A retrospective cohort study

Phillip Staibano, Michael Au, Michael Xie, Michael K. Gupta, James Edward Massey (Ted) Young, Han Zhang

Publication date 16-09-2024


Treatment de-intensification, including transoral robotic surgery (TORS), may outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Early return to work (RTW) improves quality of life in oncology patients. Our objective was to compare the RTW time in OPSCC patients undergoing primary TORS or chemoradiotherapy (CRT). We investigated the role of treatment modality on self-reported swallowing function. All patients were adults diagnosed with early-stage (T1-2, N0-2) OPSCC and treated via primary TORS or CRT. We performed 1:1 exact case matching based on tumor stage and subsite. We collected RTW outcomes for all patients. We also reported MD Anderson Dysphagia Index (MDADI) scores up to 24 months from the end of treatment. We performed statistical analyses and comparison of RTW and MDADI outcomes based on treatment group. Overall, 26 patients undergoing primary TORS and 25 undergoing primary CRT were included. We found a significant improvement in RTW in TORS patients compared to CRT (TORS: 54 days (1.8 months), IQR: 30.8; CRT: 164 days (5.4 months), IQR: 109; W=587, p = 9.28e-08) independent of HPV status, tonsillar subsite, and radiotherapy alone. Primary TORS had a 16.2-fold (95 % CI: 5.78-45.5) higher likelihood of returning to work than primary CRT patients. Primary TORS also had better MDADI scores within two years of treatment. In OPSCC, primary TORS accelerated RTW and improved swallowing when compared to primary CRT. The potential economic advantage of returning to work sooner should be discussed when reviewing treatment options with patients.

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Salivary DNA methylation derived estimates of biological aging, cellular frequency and protein expression as predictors of oral mucositis severity and survival in head and neck cancer patients

Chris P. Verschoor, Stacey A. Santi, Ravi Singh, Sujeenthar Tharmalingam, Christopher Thome, Deborah P. Saunders

Publication date 14-09-2024


Oral mucositis is a painful and debilitating condition that occurs in the majority of head and neck cancer patients receiving radiation and/or chemotherapy. While some patient and treatment related factors are known to contribute to the incidence and severity of disease, reliable biomarkers remain elusive. In the following study, we investigated the association of salivary DNA methylation derived biological aging, cellular frequency and protein concentration measures with the severity of oral mucositis and overall survival in a cohort of head and neck cancer (HNC) patients (n = 103). DNA methylation profiling was performed on saliva samples obtained prior to treatment. Biological aging measures included Horvath2, Pheno Age, Fit Age and Grim Age, and cellular frequency included epithelial and specific immune cell populations. Severe mucositis (i.e. grade 3 or 4) occurred in nearly half of patients. For malignant HNC patients (n = 84), every 1-SD increase in Grim Age was associated with 2.62-times risk of severe mucositis (95 % CI: 1.38, 5.57), while a 1-SD increase in monocyte frequency was associated with a decreased risk (OR [95 %CI]: 0.40 [0.18, 0.80]). Over a median follow-up of 53 months, 39 of 103 participants died. Six protein scores (TNFSF14, GCSF, MATN3, GDF8, nCDase, TNF-β) were associated with survival at q < 0.15. We provide evidence that the risk-related biological aging measure Grim Age may be a useful predictor of mucositis severity in HNC patients. Salivary monocyte frequency may be protective against mucositis, and this measure could be used as a predictive biomarker while also providing clues into the pathobiology of the disease.

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Development of a novel prognostic signature derived from super-enhancer-associated gene by machine learning in head and neck squamous cell carcinoma

An Wang, He Xia, Jin Li, Pengfei Diao, Jie Cheng

Publication date 09-09-2024


Dysregulated super-enhancer (SE) results in aberrant transcription that drives cancer initiation and progression. SEs have been demonstrated as novel promising diagnostic/prognostic biomarkers and therapeutic targets across multiple human cancers. Here, we sought to develop a novel prognostic signature derived from SE-associated genes for head and neck squamous cell carcinoma (HNSCC). SE was identified from H3K27ac ChIP-seq datasets in HNSCC cell lines by ROSE algorithm and SE-associated genes were further mapped and functionally annotated. A total number of 133 SE-associated genes with mRNA upregulation and prognostic significance was screened via differentially-expressed genes (DEGs) and Cox regression analyses. These candidates were subjected for prognostic model constructions by machine learning approaches using three independent HNSCC cohorts (TCGA-HNSC dataset as training cohort, GSE41613 and GSE42743 as validation cohorts). Among dozens of prognostic models, the random survival forest algorithm (RSF) stood out with the best performance as evidenced by the highest average concordance index (C-index). A prognostic nomogram integrating this SE-associated gene signature (SEAGS) plus tumor size demonstrated satisfactory predictive power and excellent calibration and discrimination. Moreover, WNT7A from SEARG was validated as a putative oncogene with transcriptional activation by SE to promote malignant phenotypes. Pharmacological disruption of SE functions by BRD4 or EP300 inhibitor significantly impaired tumor growth and diminished WNT7A expression in a HNSCC patient-derived xenograft model. Taken together, our results establish a novel, robust SE-derived prognostic model for HNSCC and suggest the translational potentials of SEs as promising therapeutic targets for HNSCC.

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The association of frailty with morbidity and mortality following major mucosal head and neck surgery

Eoin F. Cleere, Justin M. Hintze, Claire Doherty, Conrad V.I. Timon, John Kinsella, Paul Lennon, Conall W.R. Fitzgerald

Publication date 09-09-2024


Frailty refers to a state of reduced physiological reserve and functional decline. We sought to analyse whether frailty, assessed using the 5-item modified frailty index (5mFI), was associated with increased morbidity and mortality following major mucosal head and neck surgery. We performed a retrospective study of patients undergoing major mucosal head and neck surgical resection over a 2-year period. Potential confounding variables were controlled by way of multivariable regression analysis. There were 310 patients included with 77 (24.8 %) classified as frail. Most patients were male (219/310, 70.7 %), had a history of smoking (246/310, 79.4 %) and 151 patients (48.7 %) were older than 65 at time of surgery. Most surgeries related to oral cavity or oropharyngeal subsites (227/310, 73.2 %) and 150 patients (48.4 %) underwent microvascular free tissue reconstruction. On multivariable analysis, frail patients were more likely to suffer adverse outcomes such as a return to theatre (OR 3.47, 95 % CI 1.82-6.62, p < 0.001), a Clavien-Dindo grade IV complication (OR 6.23, 95 % CI 2.55-15.20, p < 0.001) or medical complications, such as respiratory complications (OR 2.61, 95 % CI 1.45-4.69; p = 0.001) or delirium (OR 5.05, 95 % CI 2.46-10.33; p < 0.001). Additionally, hospital length of stay was increased among frail patients (ß 16.46 days, 95 % CI 9.85-23.07 days; p < 0.001). Neither 90-day nor 1-year post-operative mortality was increased in frail patients. Frailty assessed using the 5mFI was associated with greater post-operative morbidity, but not mortality following major mucosal head and neck surgery.

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The first report of bilateral parapharyngeal lymph node metastasis from papillary thyroid carcinoma: A case report

Jingzhu Zhao, Xianhui Ruan, Songfeng Wei, Xiangqian Zheng, Ming Gao

Publication date 02-09-2024


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Commentary on “Platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (r/mHNSCC)”

Prithviraj T

Publication date 28-08-2024


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Challenges in treating oropharyngeal cancer in the elderly: The role of transoral surgery

Andrea Costantino, Bruce Haughey, Uthman Alamoudi, Jeffery Scott Magnuson

Publication date 26-08-2024


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Impact of antibiotics on PD-1 inhibition in recurrent/metastatic head and neck squamous cell carcinoma

Helene Knap Rabjerg, Jesper Grau Eriksen, Sebastian Søby

Publication date 26-08-2024


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Secretory carcinoma of the minor salivary gland: An in-depth case report

Reydson Alcides de Lima-Souza, Iara Vieira Ferreira, Carlos Takahiro Chone, Erika Said Abu Egal, Alena Skálová, Albina Altemani, Fernanda Viviane Mariano

Publication date 24-08-2024


A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.

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Exploring the impact of intra-tumoural heterogeneity on liquid biopsy cell-free DNA methylation and copy number in head and neck squamous cell carcinoma

Karl Payne, Harini Suriyanarayanan, Jill Brooks, Hisham Mehanna, Paul Nankivell, Deena Gendoo

Publication date 06-09-2024


Liquid biopsy profiling is gaining increasing promise towards biomarker-led identification and disease stratification of tumours, particularly for tumours displaying significant intra-tumoural heterogeneity (ITH). For head and neck squamous cell carcinoma (HNSCC), which display high levels of genetic ITH, identification of epigenetic modifications and methylation signatures has shown multiple uses in stratification of HNSCC for prognosis, treatment, and HPV status. In this study, we investigated the potential of liquid biopsy methylomics and genomic copy number to profile HNSCC. We conducted multi-region sampling of tumour core, tumour margin and normal adjacent mucosa, as well as plasma cell-free DNA (cfDNA) across 9 HNSCC patients. Collectively, our work highlights the prevalence of methylomic ITH in HNSCC, and demonstrates the potential of cfDNA methylation as a tool for ITH assessment and serial sampling.

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Preoperative protective stenting of the carotid artery in severe complex head and neck cancer resection

Ji Xiaoyu, Pan Baihong, Li Yaozhen, Chen Shen, Sheng Chang, Liu Tinghua, Ouyang Yang

Publication date 06-09-2024


To investigate effects of preoperative protective carotid artery (CA) stenting in complex head and neck cancer (HNC) resection. HNC that encases the CA is complex. Fifty-five patients diagnosed with complex HNC from 2018 to 2021 were enrolled, and were divided into Control group (general complex cases) and carotid artery stent (CAS) group (severe complex cases). All patients underwent standard tumor resection, while patients in the CAS group also underwent preoperative covered CA stenting. Medical information was retrospectively analyzed. CA stenting and tumor resection were successfully performed. Baseline demographics were recorded. CAS and Control groups had similar results for complete tumor resection rate, operation time, and intraoperative blood loss, although the CA was obviously more involved in CAS group than in Control group. However, recurrence rate in the CAS group was significantly lower than Control group, indicating that preoperative CA stent implantation facilitates complete tumor removal. Furthermore, perioperative CA-associated complications including common/internal CA ligation were more frequent in Control group. Overall survival and disease-free survival rate in CAS group and Control group was 87.5% and 69.2%, respectively. Disease-free survival rate in CAS group and Control group was 87.5% and 42.3%, respectively. No postoperative cerebral infarction was observed in either group. Overall hospitalization cost was recorded. Preoperative protective CA stenting facilitates more thorough tumor removal while better preserving the CA during complex HNC resection, reducing the surgical difficulty. Preoperative CA stenting may be a safe and effective therapeutic option for resection of HNC encasing the CA.

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Xerostomia prediction in patients with nasopharyngeal carcinoma during radiotherapy using segmental dose distribution in dosiomics and radiomics models

Xushi ZHANG, Wanjia ZHENG, Sijuan HUANG, Haojiang LI, Zhisheng BI, Xin YANG

Publication date 04-09-2024


This study aimed to integrate radiomics and dosiomics features to develop a predictive model for xerostomia (XM) in nasopharyngeal carcinoma after radiotherapy. It explores the influence of distinct feature extraction methods and dose ranges on the performance. Data from 363 patients with nasopharyngeal carcinoma were retrospectively analyzed. We pioneered a dose-segmentation strategy, where the overall dose distribution (OD) was divided into four segmental dose distributions (SDs) at intervals of 15 Gy. Features were extracted using manual definition and deep learning, applying OD or SD and integrating radiomics and dosiomics, yielding corresponding feature scores (manually defined radiomics, MDR; manually defined dosiomics, MDD; deep learning-based radiomics, DLR; deep learning-based dosiomics, DLD). Subsequently, 18 models were developed by combining features and model types (random forest and support vector machine). Under OD, O(DLR_DLD) demonstrated exceptional performance, with an optimal area under the curve (AUC) of 0.81 and an average AUC of 0.71. Within SD, S(DLR_DLD) surpassed the other models, achieving an optimal AUC of 0.90 and an average AUC of 0.85. Therefore, the integration of dosiomics into radiomics can augment predictive efficacy. The dose-segmentation strategy can facilitate the extraction of more profound information. This indicates that ScoreDLR and ScoreMDR were negatively associated with XM, whereas ScoreDLD, derived from SD exceeding 15 Gy, displayed a positive association with XM. For feature extraction, deep learning was superior to manual definition.

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Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions

Wen-Jing Yin, Wu Mao, Fang Yang, Meng-Yao Wang, Jin-Quan Liu, Dong-Ping Chen, Li-Ping Zhou, Si-Da Chen, Xi-Zhen Jiang, Yu-Meng Ou, Zheng Wu, Bin Qi

Publication date 01-09-2024


To identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. Data on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. The 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. NPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local-regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

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Immunoinhibitory effects of hypoxia-driven reprogramming of EGR1hi and EGR3 positive B cells in the nasopharyngeal carcinoma microenvironment

Yizhi Ge, Haitao Liu, Wenxuan Huang, Huanfeng Zhu, Dan Zong, Xia He

Publication date 31-08-2024


Regulatory B (Breg) cells is a type of immune cell that exhibit immunosuppressive behavior within the tumor microenvironment. However, the differentiation and regulatory mechanisms of these Breg cells remain unexplored. Single-cell transcriptome sequencing analysis of human nasopharyngeal carcinoma (NPC) revealed a significant enrichment of B cell subset characterized by high expression of EGR1 and EGR3 in the tumor microenvironment. Notably, in the hypoxic microenvironment, these B cells induce MAPK pathway activation, subsequently triggering the activation of transcription factors EGR1 and EGR3, which further modulate the expression of immunosuppressive factors like TGFB1 and IL10. In transplant experiments using primary B cells induced under hypoxia and co-transplanted with cancer cells, a significant increase in tumor growth was observed. Mechanism experiments demonstrated that EGR1

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Current state, challenges, and future perspective of adaptive radiotherapy: A narrative review of nasopharyngeal carcinoma

Xiate Zhou, Tianchi Shao, Haijian Jia, Liqiao Hou, Xingni Tang, Changhui Yu, Chao Zhou, Suna Zhou, Haihua Yang

Publication date 26-08-2024


Patients with nasopharyngeal carcinoma often experience weight loss and tumor regression during the course of radiotherapy that lasts for up to 6-7 weeks. Adaptive radiotherapy is a systematic feedback control approach based on image-guided technology that adjusts these changes and optimizes the radiotherapy plans according to new imaging findings during treatment. There is growing evidence that adaptive radiotherapy can reduce side effects, improve the quality of life, and enhance disease control. However, the routine application of adaptive radiotherapy for nasopharyngeal remains relatively limited. This review discusses the necessity, clinical benefits, and limitations of adaptive radiotherapy, and presents the current state, challenges, and future perspective of adaptive radiotherapy strategies for nasopharyngeal carcinoma.

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Comparative dosimetric analysis of normal brain tissue in patients with Nasopharyngeal carcinoma at different stages after radiation therapy

Fenglei Du, Kainan Shao, Yiwei Yang, Xue Bai, Yonghong Hua, Guoping Shan

Publication date 24-08-2024


Radiotherapy (RT) is the main treatment for patients with nasopharyngeal carcinoma (NPC). NPC patients at different stages have varying levels of damage to normal brain tissue after RT. No study has yet thoroughly analyzed the variations in radiation dosages in the brain for different stages of NPC patients treated with RT. This study aims to examine these variations. 1446 NPC patients' CT and RTdose data were retrospectively reviewed. Analysis of the radiation dosage was executed on these 803 patients. The RTdose images for several patient groups were averaged after registering each patient's RTdose data to the CT brain template created in our earlier study. The voxel-based (VB) analysis was used to examine the dose variations in the brains of three groups of NPC patients: the early-stage group, the stage III group, and the stage IV group. As the disease progresses from early to advanced stages, the intensity and volume of radiation in the brain increase. The normal brain tissue accepted a substantially larger dosage in more advanced NPC patients. Differences in brain regions between stage III and early-stage patients were minimal compared to any other two groups. Brain regions exhibited substantial variations between the stage IV group and all other patient groups were broadly distributed. Our findings highlight the critical role of NPC staging in the therapeutic strategy, emphasizing the heterogeneity of radiation-induced tissue damage across disease stages and implying the need to develop stage-specific RT plans.

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The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy

Sulaiman Alsheikh, Jie Su, Brian O’Sullivan, Jolie Ringash, John N Waldron, Scott V Bratman, John Cho, Enrique Sanz Garcia, Anna Spreafico, John de Almeida, Ezra Hahn, Andrew Hope, Ali Hosni, John Kim, Andrew McPartlin, Jillian Tsai, Tong Li, Wei Xu, Eugene Yu, Shao Hui Huang

Publication date 23-08-2024


Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC. Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders. A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately. Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification.

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Prognostic implications of lymph node yield in pediatric patients with N1b papillary thyroid cancer

Yizhuo Wei, Liu Xiao, Lina Liu, Lei Shi, Yu Wang, Bin Liu

Publication date 23-08-2024


To investigate whether lymph node (LN) yield influences clinical outcomes for pediatric patients with laterocervical lymph node metastasis (N1b) from papillary thyroid cancer (PTC). Conducted from January 1, 2008, to December 31, 2022, this was a cohort study of pediatric patients (aged ≤ 18 years) with N1b PTC who underwent total thyroidectomy and therapeutic LN dissection in the central and lateral compartments at 3 hospitals in southwest China in 2008-2021, with follow-up until 2022. Patients with distant metastasis were excluded. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with persistent/recurrent diseases. A total of 102 pediatric patients (median [range] age, 16 [6-18] years) were analyzed: 36 patients (35 %) with T1; 27 patients (26 %), T2; 18 patients (18 %), T3; and 21 patients (21 %), T4. During a median follow-up of 50 months (range, 12-154 months), persistent diseases occurred in 40 (39 %) patients. Receiver operating characteristic analysis identified LN yield cut-off (<42 LNs) to predict persistent diseases. Multivariate analysis revealed that a less-extensive lymphadenectomy (<42 LNs) was an independent risk factor for persistent diseases (hazard ratio, 2.4; 95 % confidence intervals, 1.09-5.29; P=.029). Our study highlights that a higher LN yield may favorably influence prognosis in pediatric patients with N1b PTC.

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Results of CO2 laser surgery in laryngeal papillomatosis

Paweł Solarz, Hanna Mackiewicz–Nartowicz, Anna Sinkiewicz, Paweł Burduk

Publication date 21-08-2024


Recurrent respiratory papillomatosis is medical condition strictly connected with HPV infection of the epithelium of the upper respiratory track. The main treatment of lesions located in larynx or lower pharynx includes microsurgical excision by using CO2 laser. A thorough preoperative assessment of patients is extremely important, which should not only be based on traditional laryngological examination, but also on endoscopy of the larynx and the use of the NBI (narrow band imaging) technique to assess the vascularization of lesions. In patients with recurrent papillomas, neoadjuvant therapy with antiviral agents or agents that inhibit angiogenesis is also often used. Among our group of 31 patients with laryngeal papillomas, 15 people (48%) required repeated surgical intervention and additional antiviral therapy while 10 (33%) people had to undergo the procedure three or more times due to disease recurrence. In this article we will discuss that laryngeal microsurgery with a CO2 laser is an effective method of treating patients with laryngeal papillomatosis and we will present the possibilities of adjuvant therapy.

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Circulating tumor tissue modified viral (TTMV)-HPV DNA in Recurrent, metastatic HPV-driven oropharyngeal cancer

Glenn J. Hanna, Jamie Jabalee, John N. Lukens, Lova Sun, Eleni M. Rettig, Rocco Ferrandino, Marshall R. Posner, Krzysztof J. Misiukiewicz, David M. Routman, Kathryn M. Van Abel, Catherine Del Vecchio Fitz, Scott A. Roof

Publication date 20-08-2024


Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC. This retrospective observational cohort study included 80 patients from 4 academic centers with R/M HPV+OPSCC if they had ≥ 1 plasma TTMV-HPV DNA test obtained at any point during their R/M disease course. Physician-reported clinical data and treatment history were captured in a centralized database, along with investigator-assessed response to therapy and survival. Descriptive statistics and non-parametric tests of association were employed along with survival analyses (Kaplan-Meier method). Sixteen (20 %) patients had ≥ 5 test results over time. Consecutive TTMV-HPV DNA tests were performed a median of 73 days apart. Median TTMV-HPV DNA scores were higher with an increasing per-patient number of metastatic sites (<2 vs. 2+; p < 0.01). Score changes over time were influenced by R/M treatment modality and became undetectable in 67 % (12/18) of patients who achieved a complete response to R/M therapy. Patients with detectable scores at last follow-up had significantly worse survival compared with those who were undetectable (log-rank test, p < 0.01). TTMV-HPV DNA appears useful as a prognostic tool for monitoring response to therapy in the R/M setting. In the future, TTMV-HPV DNA could be explored as an exploratory clinical trial endpoint in the metastatic setting.

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Platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC)

Lova Sun, Roger B. Cohen, A. Dimitrios Colevas

Publication date 20-08-2024


Pembrolizumab +/- chemotherapy is standard therapy for r/m HNSCC. Despite regulatory approval of platinum/5FU/pembrolizumab, a taxane is often substituted for 5FU for convenience and tolerability. We aimed to characterize nationwide use patterns and compare outcomes between platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab. Patients in a US nationwide database with r/m HNSCC treated from 2017 to 2022 with pembrolizumab plus platinum chemotherapy were included. Demographic and cancer-specific characteristics were summarized. Overall survival (OS) was estimated using Kaplan-Meier methodology, and compared between groups using log-rank test and multivariable Cox regression. Time on treatment, number of cycles, receipt of second-line therapy, and toxicities were compared between groups. Of 438 patients, 320 (73 %) received 5FU and 118 (27 %) received a taxane. Taxane use became more frequent over time and was higher in academic vs community practices (51 % vs 23 %, p < 0.001). OS did not differ between taxane and 5FU groups (mOS 12.2 vs 13.4 months, p = 0.662). On multivariable Cox regression, HR for death associated with taxane vs 5FU was 0.99 (95 %CI 0.71-1.38). Receipt of 2L therapy was numerically higher for 5FU patients (46 %) compared to taxane patients (35 %, p = 0.071). Grade ≥ 3 anemia was more common in taxane patients (33 % vs 20 %, p = 0.003), whereas grade ≥ 3 lymphopenia and thrombocytopenia were numerically higher in 5FU patients. In patients with r/m HNSCC undergoing chemoimmunotherapy, taxane vs 5FU use varies by practice setting and geographical region. Platinum/taxane/pembrolizumab was associated with similar survival as platinum/5FU/pembrolizumab; these results suggest that chemoimmunotherapy with taxane is a reasonable alternative to 5FU.

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Tumor habitat-based MRI features assessing early response in locally advanced nasopharyngeal carcinoma

Jinling Yuan, Mengxing Wu, Lei Qiu, Weilin Xu, Yinjiao Fei, Yuchen Zhu, Kexin Shi, Yurong Li, Jinyan Luo, Zhou Ding, Xinchen Sun, Shu Zhou

Publication date 17-08-2024


The early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. A total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression.
Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Among the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). The combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.

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Gemcitabine, capecitabine, and tislelizumab in recurrent/metastatic nasopharyngeal carcinoma following prior anti-PD-1 therapy failure: A retrospective study

Rui Yang, Ruichen Li, Xiaoshuang Niu, Yang Zhao, Li Yan, Shu Tian, Yi Zhu, JianJian Qiu, Xiaoshen Wang

Publication date 15-08-2024


To evaluate the effectiveness and safety of low-dose gemcitabine and metronomic capecitabine in combination with tislelizumab for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who have previously received other anti-PD-1 therapies. This retrospective, observational study included patients with RM-NPC who had prior treatment with anti-PD-1 therapy and subsequently received tislelizumab along with low-dose gemcitabine and metronomic capecitabine between March 2019 and August 2023. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Among 25 eligible patients, 8 (20%) achieved a complete response (CR). The objective response rate (ORR) was 68%, and the disease control rate (DCR) was 80%. The 1-year PFS rate was 78%. All patients experienced treatment-related adverse events, which were all grade 1 or 2. The combination of tislelizumab with low-dose gemcitabine and metronomic capecitabine demonstrated promising antitumor effectiveness in RM-NPC patients who had failed previous anti-PD-1 therapy, with a manageable safety profile.

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Survival, Surgical, and functional outcomes of transoral laser microsurgery for cT1-T3 supraglottic laryngeal Cancers: A systematic review

Jerome R. Lechien, Stéphane Hans

Publication date 03-09-2024


This review aimed to investigate the surgical, functional, and oncological outcomes of transoral laser microsurgery supraglottic laryngectomy (TOLM-SGL) for cT1-T3 laryngeal cancers. Pub Med, Scopus, and Cochrane Library were searched by two independent investigators for studies investigating the surgical, functional, and oncological outcomes of TOLM-SGL using the PRISMA statements. A bias analysis was carried out with MINORS. Twenty-four studies were included (937 patients), including 206 (25.9 %) cT1, 467 (58.7 %) cT2, and 123 (15.4 %) cT3 cases. Most patients were cN0 (63.9 %). The mean hospital stay of TOLM was 10.1 days. Aspiration (5.5 %), and bleeding (5.3 %) were the most prevalent complications. The laryngeal preservation rate was 93.7 %. Temporary tracheotomy was performed in 18.0 % of patients, with a mean time of decannulation of 6.8 days. A feeding tube was placed in 59.9 % of patients. The oral diet restarted after 6.4 days. Definitive gastrostomy was necessary in 2.4 % of cases. The 5-year OS and DFS were 70.1 % and 82.0 %, respectively. Distant metastasis, local, and regional recurrence occurred in 4.6 %, 11.6 %, and 5.1 % of patients. There was an important heterogeneity between studies for inclusion criteria, patient profiles, TOLM indications, and details of surgical, functional, and oncological outcomes. TOLM supraglottic laryngectomy is a safe, and effective procedure associated with adequate functional, surgical, and oncological outcomes. Future studies are needed to define the place of TOLM in advanced LSCC; the role and timing of concomitant bilateral neck dissection, the indications of tracheotomy and feeding tube.

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The role of microbiota in nasopharyngeal cancer: Where do we stand?

Sumel Ashique, Mohammad Houshyari, Anas Islam, Radheshyam Pal, Shakira Ghazanfar, Farzad Taghizadeh-Hesary

Publication date 18-08-2024


Nasopharyngeal carcinoma (NPC) is a common head and neck cancer with a poor prognosis. One of the crucial challenges regarding NPC is its pathogenesis. Recent findings highlight the significance of host microbiota in the development of NPC, affected locally by nasopharyngeal microbiota or remotely by oral microbiota. The oral microbiota can migrate to the nasopharyngeal space, thereby impacting the composition of the nasopharyngeal microbiota. Specific bacterial strains have been linked to the development of nasopharyngeal cancer, including Neisseria, Staphylococcus, Leptotrichia, Staphylococcaceae, Granulicatella, Corynebacterium, Fusobacterium, and Prevotella. Several mechanisms have been proposed to elucidate how microbiota dysbiosis contributes to the development of NPC, including triggering tumor-promoting inflammation, reactivating the Epstein-Barr virus (EBV), inducing oxidative stress, weakening the immune system, and worsening tumor hypoxia. In addition, the composition of nasopharyngeal microbiota and the number of tumor-infiltrating microbiota can influence the prognosis and treatment response in patients with NPC. To the best of our knowledge, this is the first review discussing the impacts of the host microbiota on nasopharyngeal cancer pathogenesis, progression, and treatment response.

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Localized intratumoral delivery of immunomodulators for oral cancer and oral potentially malignant disorders

Nourhan I. Hussein, Andrea H. Molina, Gemalene M. Sunga, Moran Amit, Yu Leo Lei, Xiao Zhao, Jeffrey D. Hartgerink, Andrew G. Sikora, Simon Young

Publication date 14-08-2024


Immunotherapy has developed into an important modality of modern cancer treatment. Unfortunately, checkpoint inhibitor immunotherapies are currently delivered systemically and require frequent administration, which can result in toxicity and severe, sometimes fatal, adverse events. Localized delivery of immunomodulators for oral cancer and oral potentially malignant disorders offers the promise of maximum therapeutic potential and reduced systemic adverse effects. This review will discuss the limitations of current standard-of-care systemic therapies and highlight research advances in localized, intratumoral delivery platforms for immunotherapy for oral cancer and oral potentially malignant disorders.

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DNA Methylation Mediated Epigenetic Silencing of PD-1 and PD-L1: Therapeutic Implications in Oral Cancer

Monisha Prasad

Publication date 26-08-2024


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