Oral Oncology 2024-03-27

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study

Ruey-Long Hong, Chia-Jui Yen, Ming-Yu Lien, Rebecca Cheng, Yu-Wen Su, Han-Nan Lin, Song Ling Poon, Chih-Yen Chien

Publication date 24-03-2024


This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

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Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects

Joshua D. Smith, Shaum S. Sridharan, Kevin J. Contrera, Jeremy D. Richmon, Allen L. Feng, Steven B. Chinn, Molly E. Heft-Neal, Matthew E. Spector

Publication date 24-03-2024


Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30 years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.

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How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group

M. Ferrari, F. Mularoni, S. Taboni, E. Crosetti, C. Pessina, A.L.C. Carobbio, N. Montalto, F. Marchi, A. Vural, A. Paderno, S. Caprioli, P. Gaudioso, M. Fermi, F. Rigoni, T. Saccardo, G. Contro, A. Ruaro, A. Lo Manto, C. Varago, M. Baldovin

Publication date 24-03-2024


In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

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Human Papilloma Virus-16 associated primary adenocarcinoma of the tonsil: Report of two cases and literature review

Anthony Waton, Anne Chambers, Hannah Fox, James OHara, Muhammad Shahid Iqbal

Publication date 20-03-2024


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In reply to Melachuri et al. (https://doi.org/10.1016/j.oraloncology.2024.106703)

Erkan Topkan, Efsun Somay, Uğur Selek

Publication date 20-03-2024


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Challenges in the diagnosis of oral squamous cell carcinoma mimicking medication-related osteonecrosis of the jaws: a multi-hospital-based case series

Rodolfo Mauceri, Martina Coppini, Mario Pérez-Sayáns, Corrado Toro, Rita Vitagliano, Giuseppe Colella, Vito Rodolico, Giuseppina Campisi

Publication date 20-03-2024


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Does a biopsy improve the diagnosis of oral lichen planus and management of the patient? In which scenario does the malignant transformation matter most?

Dante Migliari

Publication date 17-03-2024


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Comment on “advancing oral cancer diagnosis in Brazil: Integrating artificial intelligence with Teledentistry for Better Patient Outcomes”

Paulo Ricardo Elias de Melo, Mariana Agra Monteiro, Natália Vitória de Araújo Lopes, John Lennon Silva Cunha

Publication date 17-03-2024


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Association between COVID 19 exposure and expression of malignant pathological features in oral squamous cell carcinoma: A retrospective cohort study

Yufei Hua, Pingchuan Ma, Chunjie Li, Ning Gao, Zhangfan Ding

Publication date 16-03-2024


To analyze the relationship between the clinical and pathological characters of OSCC and COVID 19 exposure. A retrospective cohort study in patients with OSCC with or without COVID 19 was performed. A total of 200 OSCC patients treated with surgery from 2019 to 2023 were included. Clinical and pathological features were analysed between two groups. Characters with statistical difference were further analysed by performing univariate analysis and logistic regression analysis. The expression of Ki67 (n = 57, 71.3 %, P < 0.001) and CyclinD1 (n = 64, 80 %, P < 0.001) in OSCC with the exposure history of COVID 19 is higher than that in patients never exposed to COVID 19. COVID 19 exposure history is an independent influencing factor for higher expression of Ki67 (OR = 4.04, 95 % CI: 1.87-8.72, P < 0.001) and CyclinD1 (OR = 5.45, 95 % CI: 2.56-11.60, P < 0.001). COVID 19 may suggest more invasive malignant biological behavior of cancer cells in OSCC.

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Comment on “A case report on a nasal and oral cavity involving large solitary fibrous tumor and comprehensive review of case literature”

John Lennon Silva Cunha, Bruno Augusto Benevenuto de Andrade, Jorge Esquiche León

Publication date 16-03-2024


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Exosomal immune checkpoint protein (PD-L1): Hidden player in PD-1/PD-L1 blockade immunotherapy resistance in oral cancer

Jeevitha Rajanathadurai, Jospin Sindya, Inamul Hasan Madar, Elumalai Perumal

Publication date 13-03-2024


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Role of telemedicine in head neck cancer

Shrikant B. Mali

Publication date 10-03-2024


Chemo-radiotherapy and head and neck cancers are common adverse outcomes that impact patients' quality of life. The increasing cancer incidence and healthcare service shortages necessitate new strategies for optimal treatments and follow-ups. Digitalized healthcare, including digital health, telemedicine, and telemonitoring, is promising. HNC requires multidisciplinary team intervention, including speech language pathology telepractice models. Mobile health-based interventions can help cancer survivors increase physical activity and improve rehabilitation services. Effective self-management skills can improve outcomes. Advancements in communication technologies have led to telecommunication-based interventions incorporating swallowing exercises, education, monitoring, feedback, self-management, and communication. Home-based remote rehabilitation is urgent, especially during the COVID-19 pandemic, but the optimal strategy and effectiveness of remote interventions remain unclear. Telehealth interventions represent a possible novel approach to increase access to care across the cancer continuum, strengthen patients' knowledge and self-management, provide continuity of services, and enable remote monitoring of symptoms and response to treatment. Telehealth patients are typically younger, more likely to be English-speaking, and more likely to be female. These disparities widened slightly after the start of the pandemic but were also present prior to the pandemic.

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The utility of ultrasonographic surveillance in management of a presumed branchial cleft cyst later confirmed HPV-associated oropharyngeal cancer

Tatiana Ferraro, Alisha R. Pershad, Shaleen Arora, Esther Lee, Arjun Joshi

Publication date 10-03-2024


While branchial cleft cysts are often considered benign pathologies, the literature discusses cases of squamous cell carcinoma (SCC) arising from these cystic lesions as either a primary or metastatic tumor. We illustrate our institutional experience and review the current literature to identify recommendations for best diagnostic, surveillance, and treatment guidelines for SCC identified in a branchial cleft cyst. A 61-year-old male presented with a right sided neck mass, with suspicion of a branchial cleft cyst due to benign findings on fine needle aspiration. Following surgical excision, a focus of SCC was found on surgical pathology. Despite PET/CT and flexible laryngoscopy, no primary tumor was identified prompting routine surveillance every 3 months with cervical ultrasonography and flexible nasolaryngoscopy. Two and a half years following his initial presentation, pathologic right level II lymphadenopathy was detected on ultrasound without evidence of primary tumor. Subsequent transoral robotic surgery with right tonsillectomy and partial pharyngectomy, with right lateral neck dissection revealed a diagnosis of pT1N1 HPV-HNSCC and he was referred for adjuvant chemotherapy and radiation. To our knowledge there are less than 10 cases of confirmed HPV-associated oropharyngeal SCC arising from a branchial cleft cyst. Here we demonstrate the utility of ultrasound as a surveillance tool and emphasize a higher index of suspicion for carcinoma in adult patients with cystic neck masses.

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Atezolizumab plus bevacizumab in advanced Merkel cell carcinoma: A prospective study

L. Guimaraes de Sousa, S. Liu, P. Bhosale, M. Altan, W. Darbonne, K. Schulze, S. Dervin, C. Yun, A. Mahvash, A. Verma, A. Futreal, S. Gite, E. Parra Cuentas, W.C. Cho, I. Wistuba, J.C. Yao, S.E. Woodman, D.M. Halperin, R. Ferrarotto

Publication date 10-03-2024


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Advancing oral cancer diagnosis in Brazil: Integrating artificial intelligence with teledentistry for enhanced patient outcomes

Lucas Alves da Mota Santana, Lara Góis Floresta, Êmilly Victória Maciel Alves, Lucas Morais Rodrigues Melo, Rammom Rocha Tavares Ferreira, Graziane Ribeiro Couto, José Alcides Almeida de Arruda, Carolina Vieira Valadares, Gina Delia Roque-Torres, Gilmagno Amado Santos, Rajiv Gandhi Gopalsamy, Paulo Ricardo Martins-Filho, Lysandro Pinto Borges

Publication date 09-03-2024


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Head and neck oncology professionals’ perceptions of suicide risk screening among patients

Eric Adjei Boakye, Kevin J. Sykes, Jessica L. Hamilton, Elizabeth D. Cash, Nicole M. Duffy, Stacey Maurer, Amy M. Williams

Publication date 26-02-2024


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Comments on the article titled “Factors associated with unknown primary status in head and neck squamous cell carcinoma”: Is the N status the overlooked elephant in the room?

Giuseppe Fancello, Serena Jiang, Giuseppe Licci, Oreste Gallo

Publication date 23-02-2024


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Radiation Therapy Oncology Group 8502 “QUAD shot” regimen using volumetric modulated arc therapy for incurable head and neck cancer

Ryo Toya, Yoshiyuki Fukugawa, Tetsuo Saito, Tomohiko Matsuyama, Ryoji Yoshida, Daizo Murakami, Yorihisa Orita, Hideki Nakayama, Natsuo Oya

Publication date 23-03-2024


We aimed to evaluate the outcomes of the Radiation Therapy Oncology Group 8502 "QUAD shot" regimen using volumetric modulated arc therapy (VMAT) for incurable head and neck cancer (HNC). We included 105 patients with HNC in the study, undergoing at least one QUAD shot regimen cycle. We planned the radiotherapy using VMAT with 6 MV photons. One QUAD shot cycle included 14.8 Gy in 4 fractions with at least 6-hour intervals over 2 consecutive days, repeated every 3-6 weeks up to 3 cycles. We completed 1, 2, and 3 cycles in 11 (10 %), 17 (16 %), and 77 (73 %) patients, respectively. We concurrently performed systemic therapy in 13 (12 %) patients. Tumor response was observed in 92 (88 %) patients and at least one symptom relief in 51 (71 %) of 72 patients. We observed an overall response (tumor response or symptom relief) in 98 (93 %) patients with all patients who completed 3 cycles achieving it. The median overall survival (OS) was 6.8 months. Our multivariate analysis revealed that non-squamous cell carcinoma (p < 0.001), T category of 0-2 (p = 0.021), and 3 QUAD shot cycles (p < 0.001) were independent prognostic factors of better OS. We observed Grade 3 toxicity in 2 (2 %) patients while no ≥ Grade 4 acute or ≥ Grade 3 late toxicity. The QUAD shot regimen using VMAT exerts appropriate palliative effect in patients with incurable HNC. Treatment with higher QUAD shot cycle number would be recommended for better treatment outcomes.

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Twelve years after: The french national network on rare head and neck tumours (REFCOR)

Cassandre Gasne, Sarah Atallah, Etienne Dauzier, Juliette Thariat, Nicolas Fakhry, Benjamin Verillaud, Marion Classe, Sebastien Vergez, Antoine Moya-Plana, Valerie Costes-Martineau, Christian Righini, Ludovic de Gabory, Laurence Digue, Charles Dupin, François Régis Ferrand, Caroline Even, Bertrand Baujat, On behalf of REFCOR members

Publication date 22-03-2024


Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. A total of 7208 patients were included over a period of 10 years.
The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

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Immunotherapy time of infusion impacts survival in head and neck cancer: A propensity score matched analysis

Daniel A. Ruiz-Torres, Saskia Naegele, Archana Podury, Lori Wirth, Sophia Z. Shalhout, Daniel L. Faden

Publication date 21-03-2024


The adaptive immune response is physiologically regulated by the circadian rhythm. Data in lung and melanoma malignancies suggests immunotherapy infusions earlier in the day may be associated with improved response; however, the optimal time of administration for patients with head and neck squamous cell carcinoma (HNSCC) is not known. We aimed to evaluate the association of immunotherapy infusion time with overall survival (OS) and progression free survival (PFS) in patients with HNSCC in an Institutional Review Board-approved, retrospective cohort study. 113 patients met study inclusion criteria and 98 patients were included in a propensity score-matched cohort. In the full unmatched cohort (N = 113), each additional 20 % of infusions received after 1500 h conferred an OS hazard ratio (HR) of 1.35 (95 % C.
I.1.2-1.6; p-value = 0.0003) and a PFS HR of 1.34 (95 % C.
I.1.2-1.6; p-value < 0.0001). A propensity score-matched analysis of patients who did or did not receive ≥20 % of infusions after 1500 h showed that those who were administered ≥20 % of infusions after 1500 h trended towards a shorter OS (HR = 1.35; p-value = 0.26) and a shorter PFS (HR = 1.57, 95 % C.
I. 1.02-2.42, p-value = 0.04). Each additional 20 % of infusions received after 1500 h remained robust in the matched cohort multivariable analysis and was associated with shorter OS (adjusted HR = 1.4 (95 % C.
I.1.2-1.8), p-value < 0.001). Patients with advanced HNSCC who received more of their infusions in the afternoon were associated with shorter OS and PFS and scheduling immunotherapy infusions earlier in the day may be warranted.

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Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma

Eduardo A. Dal Lago, Luana G. Sousa, Zixi Yang, Camilla O. Hoff, Flavia Bonini, Matthew Sawyer, Kaiwen Wang, Whitney Lewis, Kareem A. Wahid, Ehab Y. Hanna, Adel El-Naggar, Clifton D. Fuller, Suprateek Kundu, Myrna Godoy, Renata Ferrarotto

Publication date 21-03-2024


Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

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MYB alternative promoter activity is increased in adenoid cystic carcinoma metastases and is associated with a specific gene expression signature

Junchi Huang, André Fehr, Fredrik Jäwert, Jonas A. Nilsson, Luc G.T. Morris, Göran Stenman, Mattias K. Andersson

Publication date 18-03-2024


Adenoid cystic carcinoma (ACC) is a head and neck cancer with a poor long-term prognosis that shows frequent local recurrences and distant metastases. The tumors are characterized by MYB oncogene activation and are notoriously unresponsive to systemic therapies. The biological underpinnings behind therapy resistance of disseminated ACC are largely unknown. Here, we have studied the molecular and clinical significance of MYB alternative promoter (TSS2) usage in ACC metastases. MYB TSS2 activity was investigated in primary tumors and metastases from 26 ACC patients using RNA-sequencing and quantitative real-time PCR analysis. Differences in global gene expression between MYB TSS2 high and low cases were studied, and pathway analyses were performed. MYB TSS2 activity was significantly higher in ACC metastases than in primary tumors (median activity 15.1 vs 3.0, P = 0.0003). MYB TSS2 high ACC metastases showed a specific gene expression signature, including increased expression of multi-drug resistance genes and canonical MYB target genes, and suppression of the p53 and NOTCH pathways. Collectively, our findings indicate that elevated MYB TSS2 activity is associated with metastases, potential drug resistance, and augmented MYB-driven gene expression in ACC. Our study advocates the need for new therapies that specifically target MYB and drug resistance mechanisms in disseminated ACC.

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Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness

Kazumasa Moriwaki, Yusuke Ayani, Hiroko Kuwabara, Tetsuya Terada, Masaaki Higashino, Ryo Kawata

Publication date 14-03-2024


Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC).
SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.

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Human papillomavirus (HPV) load is higher in HPVDNA/p16 positive than in HPVDNA positive/p16 negative oropharyngeal squamous cell carcinoma but does not differ significantly between various subsites or correlate to survival

Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Monika Lukoseviciute, Cecilia Jylhä, Linda Marklund, Anders Näsman, Lars Sivars, Tina Dalianis

Publication date 11-03-2024


Patients with human papillomavirus DNA positive (HPVDNA To address these issues HPV viral load was determined by HPV digital droplet (dd) PCR in tumor biopsies with previously known HPVDNA/p16 status from 270 OPSCC patients diagnosed 2000-2016 in Stockholm, Sweden. More specifically, of these patients 235 had HPVDNA We found that HPVDNA To conclude, the mean viral load in HPVDNA

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Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

Chung-Jan Kang, Li-Yu Lee, Shu-Hang Ng, Chien-Yu Lin, Kang-Hsing Fan, Wen-Cheng Chen, Jin-Ching Lin, Yao-Te Tsai, Shu-Ru Lee, Chih-Yen Chien, Chun-Hung Hua, Cheng Ping Wang, Tsung-Ming Chen, Shyuang-Der Terng, Chi-Ying Tsai, Hung-Ming Wang, Chia-Hsun Hsieh, Chih-Hua Yeh, Chih-Hung Lin, Chung-Kan Tsao

Publication date 10-03-2024


While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

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Trends and predictors of unplanned hospitalization among oral and oropharyngeal cancer patients; an 8-year population-based study

Masoud MiriMoghaddam, Babak Bohlouli, Hollis Lai, Shefali Viegas, Maryam Amin

Publication date 10-03-2024


The incidence of oral cancers, particularly HPV-related oropharyngeal cancer, is steadily increasing worldwide, presenting a significant healthcare challenge. This study investigates trends and predictors of unplanned hospitalizations for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients in the province of Alberta, Canada. This retrospective, population-based, cohort study used administrative data collected from all hospitals in the province. Using the Alberta Cancer Registry (ACR), a cohort of adult patients diagnosed with a single primary OCC or OPC between January 2010 and December 2017 was identified. Linking this cohort with the Discharge Abstract Database (DAD), trends in hospitalizations, primary diagnoses, and predictors of unplanned hospitalization (UH) and 30-day unplanned readmission were analyzed. Of 1,721 patients included, 1,244 experienced 2,228 hospitalizations, with 48 % being categorized as UH. The UHs were significantly associated with a higher mortality rate, 18.5 % as compared to 4.6 % for planned, and influenced by sex, age groups, comorbidities, cancer types, stages, and treatment modalities. The rate of UH per patient decreased from 0.69 to 0.54 visits during the study period (P = 0.02). Common diagnoses for UH were palliative care and post-surgical convalescence, while surgery-related complications such as infection and hemorrhage were frequent in 30-day unplanned readmissions. Predictors of UH included cancer stage, material deprivation, and treatment, while cancer type and comorbidity predicted readmissions. The rate of UHs showed a noteworthy decline in this study, which could be a result of enhanced care coordination. Furthermore, identified primary diagnosis and predictors associated with UHs and readmissions, provide valuable insights for enhancing the quality of care for cancer patients.

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Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study

Dong Hyun Kim, Seung Taek Lim, Hye Ryun Kim, Eun Joo Kang, Hee Kyung Ahn, Yun-Gyoo Lee, Der Sheng Sun, Jung Hye Kwon, Sang-Cheol Lee, Hyun Woo Lee, Min Kyoung Kim, Bhumsuk Keam, Keon-Uk Park, Seong-Hoon Shin, Hwan Jung Yun

Publication date 09-03-2024


This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab.
We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

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Clinical features and prognostic factors of nasopharyngeal carcinoma with brain metastases

Kehui Chen, Mengting Shi, Silang Mo, Tingting Liu, Yuanyuan Zhao, Li Zhang, Shen Zhao

Publication date 09-03-2024


Brain metastasis in nasopharyngeal carcinoma is a rare occurrence, and the characteristics of patients in this subgroup remain poorly defined. This study aims to delineate the clinical features, treatment modalities, prognostic factors, and survival of nasopharyngeal carcinoma patients with brain metastasis. A retrospective analysis was conducted on patients diagnosed with nasopharyngeal carcinoma who developed brain metastasis and were treated at the Sun Yat-sen University Cancer Center between July 2000 and July 2023. Clinical data from patients were collected and used to assess their survival after brain metastases and prognostic factors. Among 82,434 nasopharyngeal carcinoma patients, 40 (0.06 %) developed Brain metastasis with a median follow-up of 5.1 years. The predominant histological subtype was non-keratinizing squamous cell carcinoma (85 %). The median post-BM survival was 25 months. The age, the Eastern Cooperative Oncology Group (ECOG), and the procedural treatment of BM were prognostic factors. Notably, patients receiving local treatments had significantly prolonged post-BM survival compared to those receiving systemic therapy alone (median, 47.00 vs. 11.00 months; p = 0.011). This is the largest cohort of brain metastasis in nasopharyngeal carcinoma to date. Local therapeutic measures after brain metastasis can significantly enhance the prognosis of these patients, particularly when radiotherapy is applied.

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Evaluation of a novel model incorporating serological indicators into the conventional TNM staging system for nasopharyngeal carcinoma

Cong Ding, Dong-Yu Dai, Zi-Kang Luo, Gao-Yuan Wang, Zhe Dong, Guan-Jie Qin, Xiao-Jing Du, Jun Ma

Publication date 03-03-2024


Non-anatomical factors significantly affect treatment guidance and prognostic prediction in nasopharyngeal carcinoma (NPC) patients. Here, we developed a novel survival model by combining conventional TNM staging and serological indicators. We retrospectively enrolled 10,914 eligible patients with nonmetastatic NPC over 2009-2017 and randomly divided them into training (n = 7672) and validation (n = 3242) cohorts. The new staging system was constructed based on T category, N category, and pretreatment serological markers by using recursive partitioning analysis (RPA). In multivariate Cox analysis, pretreatment cell-free Epstein-Barr virus (cfEBV) DNA levels of >2000 copies/mL [HR Our novel RPA staging model outperformed the current TNM staging system in prognostic prediction and clinical decision-making. We recommend incorporating cfEBV DNA, LDH, and CAR into the TNM staging system.

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Identification of new head and neck squamous cell carcinoma molecular imaging targets

Jeroen E. van Schaik, Bert van der Vegt, Lorian Slagter-Menkema, Bernard F.A.M. van der Laan, Max J.H. Witjes, Sjoukje F. Oosting, Rudolf S.N. Fehrmann, Boudewijn E.C. Plaat

Publication date 01-03-2024


Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets. Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa. TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015). The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets.

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Treatment package time\xa0<\xa014\xa0weeks improves recurrence free and disease specific survival in HPV positive OPC with high-risk features

Manasa Melachuri, Chareeni Kurukulasuriya, Purva Rumde, Terral Patel, Daniel Awad, Seungwon Kim, Robert Ferris, Shaum Sridharan, Umamaheswar Duvvuri

Publication date 01-03-2024


Guidelines recommend treatment package time < 85 days and time from surgery to radiation initiation < 6 weeks in head and neck cancer patients. However, HPV positive primaries treated with TORS and adjuvant radiotherapy traditionally demonstrate favorable outcomes. Single center retrospective chart review of patients diagnosed with HPV positive treatment naïve primary squamous cell carcinoma treated with TORS and postoperative radiation therapy with or without Chemotherapy from 2012 to 2022 with data collection from December 2022-April 2023. Kaplan-Meier survival analysis with log-rank testing assessed the impact of time intervalsbetween diagnosis, TORS, radiation initiation and radiation completion on recurrence free and disease specific survival. Univariate Cox proportional hazards regression analysis was performed to identify factors associated with recurrence free and disease specific survival. Subgroup analysis was done with high risk (positive lymph nodes > 5, >1mm extracapsular extension, positive margins) patients who underwent concurrent Chemotherapy. Of 255 patients (225 males [89 %], average age 58 years, 163 [64 %] high-risk, median follow-up 4.3 years), 22 (8.6 %) had recurrence and 14 died due after disease recurrence.
Only radiation length of 5-7 weeks prolonged survival in the entire population. In the high-risk cohort, time from TORS to radiation initiation < 6 weeks improvedrecurrence free survival, while total package time < 14 weeks wasassociated with greater recurrence free and disease specific survival.

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Mutation detection in saliva from oral cancer patients

Ahmed A. Ahmed, Mateja Sborchia, Hannah Bye, Maria Roman-Escorza, Ariella Amar, Rhonda Henley-Smith, Edward Odell, Mark McGurk, Michael Simpson, Tony Ng, Elinor J. Sawyer, Christopher G. Mathew

Publication date 27-02-2024


The incidence of head and neck squamous cell carcinoma (HNSCC) continues to increase and although advances have been made in treatment, it still has a poor overall survival with local relapse being common. Conventional imaging methods are not efficient at detecting recurrence at an early stage when still potentially curable. The aim of this study was to test the feasibility of using saliva to detect the presence of oral squamous cell carcinoma (OSCC) and to provide additional evidence for the potential of this approach. Fresh tumor, whole blood and saliva were collected from patients with OSCC before treatment. Whole exome sequencing (WES) or gene panel sequencing of tumor DNA was performed to identify somatic mutations in tumors and to select genes for performing gene panel sequencing on saliva samples. The most commonly mutated genes identified in primary tumors by DNA sequencing were TP53 and FAT1. Gene panel sequencing of paired saliva samples detected tumor derived mutations in 9 of 11 (82%) patients. The mean variant allele frequency for the mutations detected in saliva was 0.025 (range 0.004 - 0.061). Somatic tumor mutations can be detected in saliva with high frequency in OSCC irrespective of site or stage of disease using a limited panel of genes. This work provides additional evidence for the suitability of using saliva as liquid biopsy in OSCC and has the potential to improve early detection of recurrence in OSCC. Trials are currently underway comparing this approach to standard imaging techniques.

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Global gene expression profile of proliferative verrucous leukoplakia and its underlying biological disease mechanisms

Camile S. Farah, Kate Shearston, Emma C. Turner, Michael Vacher, Simon A. Fox

Publication date 26-02-2024


Proliferative verrucous leukoplakia (PVL) is a rare and enigmatic oral potentially malignant disorder which almost invariably results in oral squamous cell carcinoma (OSCC). The aims of this project were to use transcriptome profiling to characterise PVL gene expression patterns for biomarker identification and gain insight into the molecular aetiopathogenesis of PVL. Forty-three oral cavity mucosal biopsies from 32 patients with oral lesions clinically compatible with either PVL or non-PVL conventional oral leukoplakia (OLK) underwent transcriptome profiling by RNA sequencing. Data was analysed by hierarchical clustering, differential gene expression, functional enrichment and network analysis, sparse partial least squares discriminant analysis sPLS-DA, and immune cell phenotypic estimation. We found 464 genes significantly differentially expressed at least 2-fold between PVL and non-PVL OLK (193 up and 271 down). HOX genes, including HOXA1 and HOXB7, keratin-associated proteins (KRTAPs) and olfactory receptor G proteins (OR) were significantly upregulated in PVL. Other upregulated genes in PVL included FOS, WNT16 and IFNA1. Pathway analysis showed that there was a significant downregulation of connective tissue signalling in PVL. Classifying multivariate models based upon 22 genes discriminated PVL from non-PVL OLK. Bioinformatic profiling showed that immune cell profiles in PVL and OLK were similar except that fibroblast markers were reduced in PVL. These results demonstrate that PVL and conventional OLK are molecularly distinct with upregulation of many cancer-associated genes. They provide insight into the pathogenesis of PVL and show that biomarker based molecular diagnostics is feasible to discriminate and inform diagnosis and management.

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Tumor volume instead of recurrent T category predicts clinical outcome of patients with locally recurrent nasopharyngeal carcinoma salvaged by carbon ion radiation therapy

Jiyi Hu, Qingting Huang, Weixu Hu, Fei Liang, Jing Gao, Jing Yang, Xianxin Qiu, Haojiong Zhang, Guangyuan Zhang, Jiade Jay Lu, Lin Kong

Publication date 23-02-2024


Although carbon ion radiation therapy (CIRT) substantially improves the overall survival (OS) of patients with LR-NPC, approximately 40% of the patients may develop local recurrence. The purpose of study is to assess the value of tumor volume (TV) as a predictive tool to guide individualized CIRT. Consecutive patients with LR-NPC treated using CIRT at Shanghai Proton and Heavy Ion Center between April 2015 and May 2019 were included. TV before CIRT was delineated and calculated. The generalized additive Cox model was used to examine the relationship between TV and OS and local progression-free survival (LPFS). A cutoff value of tumor volume was identified to best discriminate patients with different 2-year OS rates, using receiver operating characteristic (ROC) analysis. A total of 157 patients were enrolled. The median tumor volume was 22.49 (2.52-90.13) ml. In the univariable analyses, tumor volume was significantly associated with OS (p < 0.001) and LPFS (p = 0.01). The relationships with OS (p = 0.009) and LPFS (p = 0.020) remained significant in multivariable analyses. Using ROC analysis, a TV of 26.69 ml was identified to predict the 2-year OS rate. To facilitate potential clinical use, 25 ml was designated as the final cutoff value. The 2-year OS and LPFS rates were 88.6 % vs 62.3 %, and 54.7 % vs 35.5 %, for patients with a TV ≤ 25 ml and > 25 ml, respectively. Tumor volume could predict the OS and LPFS of patients. We propose that tumor volume should be considered in the risk stratification and CIRT-based treatment for patients with LR-NPC.

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Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study

Qiu-Yan Chen, Shan-Shan Guo, Ying Luo, Song Qu, De-Hua Wu, Xiao-Zhong Chen, Don-Ping Chen, Xin-Tian Qin, Qin Lin, Feng Jin, Shao-Jun Lin, Zhi-Fang Yao, Wei Liu, Zhongmin Maxwell Wang, Bai-Yong Li, Michelle Xia, Rui-Hua Xu, Lin-Quan Tang, Hai-Qiang Mai

Publication date 23-02-2024


This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

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Margin to depth of invasion ratio as an indicator for stratifying close margins in early-stage oral squamous cell carcinoma

Chun-Yang Hung, Tung-Lin Lee, Chun-Wei Chang, Cheng-Ping Wang, Mei-Chun Lin, Pei-Jen Lou, Tseng-Cheng Chen

Publication date 21-02-2024


In early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. Patients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. We analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). For early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

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Medicare dental coverage for patients with head and neck cancer: An opportunity in need of advocates

Lisa Simon, Jonathan Paly, Elyse Park, Margaret Samuels-Kalow

Publication date 17-03-2024


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Is the robot an instrument or an indication for transoral surgery?

Armando De Virgilio, David Virós Porcuna, Claudio Sampieri, Andrea Costantino

Publication date 21-02-2024


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