Oral Oncology 2021-10-23

Exophytic verrucous hyperplasia as a clinical terminology includes verrucous hyperplasia with or without epithelial dysplasia in histology

Wei Liu, Laikuan Zhu, Ling Xu, Lan Wu

Publication date 20-10-2021


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Trans-cervical mandibulotomy approach for a multi-compartmental trigeminal Schwannoma: A surgeon’s guide

Abhinav Thaduri, Rajkumar Kottayasamy Seenivasagam, Kinjal Shankar Majumdar, Shahab Ali Usmani, Dileep Dungala Maharaj, Achyuth Panuganti

Publication date 19-10-2021


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Reply: Nodal yield and topography of nodal metastases from oral cavity squamous cell carcinoma – An audit of 1004 cases undergoing primary surgical resection

Anu Joy, Vishal U.S. Rao

Publication date 19-10-2021


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The impact of positive resection margins on survival requires further study?

BhanuPrakash Bylapudi, Vishal U.S. Rao, Anand Subash, Shalini Thakur

Publication date 16-10-2021


Squamous cell carcinoma of oral cavity is usually treated by surgery followed by adjuvant treatment. In most standard cancer institutions, margin analysis is a key barometer for measuring the quality of surgical resection. Many studies reported that positive margins have at least a 50% reduction in the overall survival. The contributing factors that could improve surgical outcomes have to be explored. Patterns of outcomes in patients with positive margins can be understood better by analyzing the subsites involved. In the past, positive margins have been associated with a poor prognosis. A detailed analysis of the NCDB and other larger databases would aid in revising our practices to optimize oncological outcomes.

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Parotid metastasis of clear cell renal cell carcinoma 8\xa0years after nephrectomy

Thalita Santana, Marcos Custódio, Camila Dayla Melo Oliveira, Edelto dos Santos Antunes, Suzana Cantanhede Orsini Machado de Sousa, Fábio Daumas Nunes

Publication date 12-10-2021


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Institutional patterns of head and neck oncology care during the early phase of the COVID-19 pandemic: A retrospective, pooled cross-sectional analysis

Avni Shah, Baran D. Sumer, Kelly Schostag, Sanjana Balachandra, David J. Sher, Eli A. Gordin, Andrew T. Day

Publication date 12-10-2021


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Management of burning sensation in oral submucous fibrosis: more concerns than clarity

Sachin C. Sarode, Gargi S Sarode, Namrata Sengupta, Monal Yuwanati, Amol Gadbail, Shailesh Gondivkar, Yashwant Ingle

Publication date 12-10-2021


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Hormonal receptor evaluation in salivary duct adenocarcinoma

Sufana Shikdar, Evan Fowle, Humza Razaq, Wajeeha Razaq

Publication date 12-10-2021


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Hemangiomatous adenomatoid odontogenic tumor of maxilla: A new variant?

Sachin C. Sarode, Gargi S. Sarode, Namrata Sengupta, Urmi Ghone, Kedar Vaidya

Publication date 10-10-2021


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Skeletal muscle mass at C3 is a strong predictor for skeletal muscle mass at L3 in sarcopenic and non-sarcopenic patients with head and neck cancer

Sandra I. Bril, M.A. van Beers, N. Chargi, N. Carrillo Minulina, E.J. Smid, J.W. Dankbaar, R. de Bree

Publication date 10-10-2021


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A case of Maffucci syndrome with a buccal hemangioma harboring a mutation in IDH1

Norihisa Ichimura, Noriyuki Yamamoto, Naoto Toyama, Hideharu Hibi

Publication date 09-10-2021


Maffucci syndrome, first described in 1881, is a rare, non-hereditary skeletal disorder characterized by multiple enchondromas in combination with soft tissue hemangiomas. Recent studies have implicated somatic mutations in IDH1/2 contributing to the pathogenesis of Maffucci syndrome. This study describes the first case of Maffucci syndrome harboring a mutation in IDH1, which was associated with a hemangioma in the oral mucosa. A 32-year-old man, who was diagnosed with Maffucci syndrome during childhood, was referred to our department in April 2020 due to a mass in the left buccal mucosa. The mass was soft, dome-shaped, had dark red protrusions and well-defined borders, and the dimensions were approximately 15 × 10 mm. Magnetic resonance imaging revealed a mass with a dimension of 13 × 10 mm, which appeared hyperintense on T2-weighted images. The vascular lesion was surgically resected under local anesthesia owing to hemangioma diagnosis. We then analyzed the IDH1/2 sequences using DNA extracted from the excised tumor tissue and peripheral blood. The analysis revealed the presence of a heterozygous mutation in IDH1 in the tumor tissue, corresponding to an R132C substitution. The mutation was not present in peripheral blood DNA. After over one year of resection, the patient is presently free from tumor recurrence and is under follow-up for the early detection of recurrent hemangioma.

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Blastoid variant of mantle cell lymphoma in palatine tonsil

Vitor Bonetti Valente, Tamara Fernandes de Castro, Aline Satie Takamiya, Renata Callestini, José Cândido Caldeira Xavier-Junior, Gabriel Macedo Cortopassi, Sebastião Conrado Neto, Francisco Urbano Collado, Éder Ricardo Biasoli, Glauco Issamu Miyahara, Daniel Galera Bernabé

Publication date 06-10-2021


Blastoid variant of mantle cell lymphoma (MCL) is an aggressive and extremely rare malignancy. MCL may be diagnosed in lymph nodes and/or extranodal sites exhibiting a poor prognosis. MCL with primary presentation in palatine tonsils has been rarely reported. Herein, we report the case of a 73-year-old man with a painless nodular mass on the right palatine tonsil. A biopsy was performed, and microscopic analysis revealed a neoplasm composed of small to medium sized lymphocytes with finely dispersed chromatin, roundish nucleus and many mitoses. The tumor cells were positive for CD20 (L26), CD5 (4C7), Cyclin D1 (EP12), Bcl2 (124) and Ki-67 (MIB-1; 90%), and negative for Bcl6 (PG-B6p), MUM1 (MUM1p) and CD3 (Polyclonal). These findings led to the diagnosis of blastoid variant of MCL. Diagnostic workup with computed tomography scan excluded other sites of disease. The patient was treated successfully with cyclophosphamide, doxorubicin, vincristine and prednisolone (mini-CHOP regimen). Although the blastoid variant of MCL is rare, it should be included in the differential diagnosis of rapid-growing masses in the palatine tonsil.

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The prospective relevance of autologous platelet concentrates for the treatment of oral mucositis

Mohammad Amin Amiri, Nima Farshidfar, Shahram Hamedani

Publication date 08-10-2021


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Oral mucosal pseudotumor – Novelty complication in patient undergoing bevacizumab therapy

Adarsh Kudva, Jonathan Koshy, Joanna Grace Jacob

Publication date 01-10-2021


Medication-related osteonecrosis of the jaw (MRONJ) is a manifestation of bone exposure in the maxillofacial region due to use of drugs such as bisphosphonates, anti-resorptive agents and anti-angiogenic agents. This G1- humanized monoclonal antibody neutralizes the activity of the Vascular Endothelial Growth Factor (VEGF), thus reducing the vascularity of the tumor, which in turn, results in the inhibition of its growth. This case report is of a 53-year-old man with metastatic cholangiocarcinoma who received bevacizumab therapy for the past 11 months. Delayed healing of extraction sockets, osteosclerosis, and exposed bone in the mandible with a mucosal swelling was noted a month after extractions were done. The present case reinforces recent observations that the anti-angiogenic properties of bevacizumab may present a source of osteonecrosis of the jaw. To reduce the incidences of MRONJ, it is imperative to emphasize on preventive dental care, strict oral hygiene maintenance, and regular dental follow ups.

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Tobacco induced epithelial dysplasia at minor salivary gland excretory duct and oral cancer

Sachin C. Sarode, Gargi S. Sarode, Namrata Sengupta, Urmi Ghone

Publication date 28-09-2021


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Transoral robotic thyroidectomy: First case as a new technique in Vietnam

Quang Van Le, Duy Quoc Ngo, Hau Xuan Nguyen, Quy Xuan Ngo, Binh Van Pham

Publication date 28-09-2021


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Malignant lesion of clear cells: A diagnostic challenge of an unusual presentation mimicking a benign lesion

Maria Gabriela Rolim Silveira Sá, Henrique Bemfica de Farias Freitas, Martinho Campolina Rebello Horta, Marcelo Ferreira Cardoso Pinto, Lorenzo Duarte Testolin, Giovanna Ribeiro Souto

Publication date 21-09-2021


In the oral cavity, a broad spectrum of differential diagnostics includes lesions composed of clear cells. Under this umbrella, Clear Cell Odontogenic Carcinoma (CCOC) and Hyalinizing Clear Cell Carcinoma (HCCC) are rare malignancies that arise from different histological origins. However, the histology is similar; therefore, differentiation of CCOC and HCCC lesions is difficult and, in some cases, impossible to distinguish morphologically and immunohistochemically. Herein, we report an unusual presentation of a well-defined nodular lesion affecting the maxillary gingiva in a 19-year-old female, which presented clinically as a benign or reaction etiology lesion. Microscopic evaluation showed a tumor composed of cell sheets with clear cytoplasm, separated by septa of fibrous tissue and invading the connective tissue. Tumor cells were positive for p63 and AE1/AE3 and negative for PAX8, smooth muscle actin (AML) and estrogen receptor. The diagnosis was carcinoma with a clear cell pattern, and it was not possible to distinguish between HCCC and CCOC. In this study, clinicopathologic, histologic, and immunohistochemistry features of CCOC and HCCC were discussed due to the challenging histological diagnosis. Radical surgical treatment and rehabilitation of the patient through graft and dental implants were performed. The patient is under follow-up with no signs of recurrence.

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Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience

Ari J. Rosenberg, Nishant Agrawal, Alexander Pearson, Zhen Gooi, Elizabeth Blair, John Cursio, Aditya Juloori, Daniel Ginat, Adam Howard, Jeffrey Chin, Sara Kochanny, Corey Foster, Nicole Cipriani, Mark Lingen, Evgeny Izumchenko, Tanguy Y. Seiwert, Daniel Haraf, Everett E. Vokes

Publication date 19-10-2021


Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC.
Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30-50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.

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Long-term swallowing-related outcomes in oral cancer patients receiving proactive swallowing therapy

Wen-Hsuan Tseng, Tzu-Hsiang Li, Hsiang-Ling Chiu, Tsung-Lin Yang, Cheng-Ping Wang, Tseng-Cheng Chen, Chun-Nan Chen, Jen-Yuh Ko, Tzu-Yu Hsiao, Pei-Jen Lou

Publication date 17-10-2021


The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life (QoL) in oral cancer patients in the first two years after definitive treatment. Consecutive adult patients with locally advanced oral cancer who received radical surgery, free flap reconstruction, and adjuvant radiotherapy were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, and 24 months were evaluated. A total of 104 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in FOIS from one month, and in BW and MDADI from three months. A total of 94% patients were free of tube feeding at 12 months but with a diet requiring special preparations or compensation. Safe swallowing could be achieved in approximately 90% of the participants after six months with diet modification or compensatory maneuvers. BW at 18 and 24 months did not differ significantly from baseline. Proactive swallowing therapy is feasible for patients with locally advanced oral cancer receiving definitive treatments. It facilitates safe oral intake and adequate nutrition. Patients who performed swallowing exercises had a faster and better recovery in swallowing function and swallowing-related QoL.

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Symptom burden, quality of life, functioning and emotional distress in survivors of human papillomavirus associated oropharyngeal cancer: An Australian cohort

Lachlan McDowell, Georgina Casswell, Mathias Bressel, Allison Drosdowsky, Danny Rischin, Andrew Coleman, Sudichhya Shrestha, Ieta DCosta, Tsien Fua, Albert Tiong, Chen Liu, Karla Gough

Publication date 16-10-2021


This cross-sectional study examines patient-reported outcomes and functioning-based subgroups in human papillomavirus-associated oropharyngeal cancer survivors treated with chemoradiotherapy ≥12 months prior. Survivors completed EORTC QLQ-C30, MDASI-HN and PROMIS-Emotional distress questionnaires. Subgroups were identified via two-step clustering of QLQ-C30 functioning scales. 136 patients were enrolled. Clinicians' graded 19/136 (14%) patients as having at least one severe (Grade 3 CTCAE) toxicity, whereas 68/136 (50%) patients self-reported at least one toxicity in the severe range (MDASI-HN ≥ 7). QLQ-C30 Global health status score (mean 76, SD = 20) was comparable to population norms. Rates of moderate/severe anxiety (10%/1%) and depression (4%/1%) were low. Two functioning-based subgroups were formed based on auto-clustering statistics: high- (n = 93) and low-functioning (n = 41). Differences on all functioning scales were large (d: 1.57-2.29), as were differences on the remaining QLQ-C30 scales/items, most MDASI-HN symptom severity/interference scales, and PROMIS scales (d: 0.80-2.03). Differences and associations with patient/clinical characteristics were not significant. In this Australian cohort of HPV-OPC survivors there was significant discordance between clinician- and patient-reported toxicity. We observed population comparable global quality of life and low rates of emotional distress. However, we identified a low-functioning subgroup reporting significantly worse outcomes on a range of patient-reported measures who may benefit from targeted support.

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NGS-based miRNome identifies miR-449 cluster as marker of malignant transformation of sinonasal inverted papilloma

Massimo Re, Marco Tomasetti, Federica Monaco, Monica Amati, Corrado Rubini, Maria P. Foschini, Giacomo Sollini, Federico Gioacchini, Ernesto Pasquini, Lory Santarelli

Publication date 16-10-2021


identification of the miRNA expression profile in sinonasal inverted papilloma (SNIP) as a tool to evaluate the risk of transformation into sinonasal squamous cell carcinoma (SNSCC). paired tumour tissues and adjacent normal tissues were obtained from SNIP and SNSCC patients who had undergone surgical resection and used for next-generation sequencing (NGS)-based miRNome analysis. SNIP tissues with concomitant dysplasia (SNIP-DISP) were used as malignant transition samples. By comparing the deregulated miRNAs in SNIP and SNSCC, an miRNA cluster was identified and its physio- and clinical-pathological value was predicted. NGS identified 54 miRNAs significantly down- and upregulated in SNIP. Among them, the miR-449 cluster was upregulated in SNIP and could differentiate the benign tumour from normal tissue. Notably, the miR-449 cluster was found to be significantly underexpressed in SNSCC, and the cluster markedly changed in SNIP during the malignant transition into SNSCC. miRNA enrichment analysis and GO analysis revealed that miR-449 is involved in apoptotic and cell proliferation pathways. Our findings suggest that miR-449 may be involved in the molecular pathogenesis of SNIP and its malignant transformation into SNSCC. miR-449 might therefore be a useful tumour biomarker in patients with SNIP and may also have the potential to be used as a tool for detecting and monitoring the course of the possible malignant transformation.

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Prediction of treatment outcome using MRI radiomics and machine learning in oropharyngeal cancer patients after surgical treatment

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

Publication date 15-10-2021


In this study, we aimed to analyze preoperative MRI images of oropharyngeal cancer patients who underwent surgical treatment, extracted radiomics features, and constructed a disease recurrence and death prediction model using radiomics features and machine-learning techniques. A total of 157 patients participated in this study, and 107 stable radiomics features were selected and used for constructing a predictive model. The performance of the combined model (clinical and radiomics) yielded the following results: AUC of 0.786, accuracy of 0.854, precision of 0.429, recall of 0.500, and f1 score of 0.462. The combined model showed better performance than either the clinical and radiomics only models for predicting disease recurrence. For predicting death, the combined model performance has an AUC of 0.841, accuracy of 0.771, precision of 0.308, recall of 0.667, and f1 score of 0.421. The combined model showed superior performance over the predictive model using only clinical variables. A Cox proportional hazard model using the combined variables for predicting patient death yielded a c-index value that was significantly better than that of the model including only clinical variables. A predictive model using clinical variables and MRI radiomics features showed excellent performance in predicting disease recurrence and death in oropharyngeal cancer patients. In the future, a multicenter study is necessary to verify the model's performance and confirm its clinical usefulness.

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Nomogram-aided individual induction chemotherapy regimen selection in advanced nasopharyngeal carcinoma

Hao Peng, Lei Chen, Yan-Ping Mao, Li Tian, Li-Zhi Liu

Publication date 08-10-2021


We undertook this study to clarify how TPF, TP and PF induction chemotherapy (IC) regimens benefit for nasopharyngeal carcinoma (NPC) patients with different risk of disease progression. Patients with newly diagnosed, stage III-IVA NPC were included. A quantitative nomogram was built using the independent prognostic factors identified for disease-free survival (DFS). Patients were stratified into low-risk and high-risk groups by the nomogram. Survival outcomes and toxicities between different IC regimens were compared. In total, 1647 (41.0%), 1123 (28.0%) and 1242 (31.0%) patients received TPF, PF and TP regimen, respectively. Consequently, 2253 (56.2%) patients were clarified as low-risk group and the other 1759 (43.8%) as high-risk group. Survival outcomes did not significantly differ between TPF, PF and TP regimens within the low-risk group. However, TPF was associated with significantly improved 3-year DFS (76.2% vs. 67.5% vs. 68.3%), overall survival (88.3% vs. 84.1% vs. 83.9%), distant metastasis-free survival (81.9% vs. 75.0% vs. 77.4%) and locoregional relapse-free survival (92.0% vs. 87.5% vs. 86.9%; all P < 0.05) compared with PF and TP within high-risk group. Multivariate analysis also confirmed these findings. Toxicity analysis showed that TP regimen has the highest percentage of grade 3-5 hematologic toxicities while PF regimen achieved the lowest percentages of overall grade 3-5 adverse events. Patients with high risk should receive TPF for better efficacy and PF may be a better choice for low-risk patients with regard to less grade 3-5 toxicities.

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Germline variants in DNA repair genes are associated with young-onset head and neck cancer

Sarah Santiloni Cury, Priscila Mayrink de Miranda, Fabio Albuquerque Marchi, Luisa Matos do Canto, Thiago Celestino Chulam, Annabeth Høgh Petersen, Mads M. Aagaard, Clóvis Antonio Lopes Pinto, Luiz Paulo Kowalski, Silvia Regina Rogatto

Publication date 02-10-2021


The genetic predisposition to head and neck carcinomas (HNSCC) and how the known risk factors (papillomavirus infection, alcohol, and tobacco consumption) contribute to the early-onset disease are barely explored. Although HNSCC at early onset is rare, its frequency is increasing in recent years. Germline and somatic variants were assessed to build a comprehensive genetic influence pattern in HNSCC predisposition and patient outcome. Whole-exome sequencing was performed in 45 oral and oropharynx carcinomas paired with normal samples of young adults (≤49 years). We found FANCG, CDKN2A, and TPP germline variants previously associated with HNSCC risk. At least one germline variant in DNA repair pathway genes was detected in 67% of cases. Germline and somatic variants (including copy number variations) in FAT1 gene were identified in 9 patients (20%) and 12 tumors (30%), respectively. Somatic variants were found in HNSCC associated genes, such as TP53, CDKN2A, and PIK3CA. To date, 55 of 521 cases from the large cohort of TCGA presented < 49 years old. A comparison between the somatic alterations of TCGA-HNSCC at early onset and our dataset revealed strong similarities. Protein-protein interaction analysis between somatic and germline altered genes revealed a central role of TP53. Altogether, germline alterations in DNA repair genes potentially contribute to an increased risk of developing HNSCC at early-onset, while FAT1 could impact the prognosis.

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Weight loss and its impact on outcome in head and cancer patients during chemo-radiation

Gunjesh Kumar Singh, Vijay M. Patil, Vanita Noronha, Amit Joshi, Nandini Menon, Sarbani Ghosh Lashkar, Vijayalakshmi Mathrudev, Kavita Nawale Satam, Kumar Prabhash

Publication date 28-09-2021


Weight loss during chemotherapy and its impact on the cancer outcomes have been invariably reported in the literature. We also did a post-hoc analysis of a randomized phase III trial to see the same. The database of a recently published randomized study comparing cisplatin-radiation with nimotuzumab cisplatin-radiation was used for this analysis. Week-wise weight loss during the course of treatment was noted. The impact of severe weight loss (grade 2-3) on progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) was studied using the Kaplan Meier method. Binary logistic regression analysis was used to see the effect of various factors. Out of a total of 536 patients, weight loss was captured in 524. Out of these 524 patients, any degree of weight loss was seen in 293 (55.91%) patients. Grade 1 weight loss was noted in 192 (36.6%) patients, grade 2 in 96 (18.3%) and grade 3 in 5 (1%) patients. The 2-year PFS was 53% and 57.1% in severe and non-severe weight loss groups respectively (p-value = 0.36). The 2-year LRC was 60% in patients with severe weight loss, while it was 63.5% in those with non-severe weight loss (p-value = 0.47). The 2-year OS was 59.3% versus 62.2% in severe and non-severe weight loss cohorts respectively (p-value = 0.21). None of the factors was found to be associated with severe weight loss. Severe weight loss was uncommon in our patients. Weight loss during treatment was not associated with poor survival outcomes.

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Pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile infection following major head and neck free and pedicled flap surgeries

Tjoson Tjoa, Vinay K. Rathi, Neerav Goyal, Bharat B. Yarlagadda, Miriam B. Barshak, Debbie L. Rich, Kevin S. Emerick, Derrick T. Lin, Daniel G. Deschler, Marlene L. Durand

Publication date 27-09-2021


Medical postoperative infections (MPIs) are important causes of morbidity following major head and neck free and pedicled flap reconstruction, but the incidence, time of onset, and microbiology are not well characterized. Medical records were reviewed of all head and neck flap surgeries performed 2009-2014 at an academic medical center. Postoperative pneumonia, urinary tract infection (UTI), bloodstream infection (BSI), Clostridioides difficile (CDI), and surgical site infections (SSI) were noted. Catheter-associated UTI (CAUTI), central line-associated BSI (CLABSI), and methicillin-resistant Staphylococcus aureus (MRSA) BSI were also evaluated. Following 715 free (540) or pedicled (175) flap surgeries, 14.1% of patients developed ≥one MPI including pneumonia (10.6%), UTI (2.1%), BSI (0.7%), and CDI (2.4%). Onset was ≤7 days in 77%. The MPI incidence in free vs pedicled flaps was similar. By multivariate analysis, age ≥65 and clindamycin perioperative prophylaxis were associated with increased MPI risk, clean class surgery with decreased risk. The incidence of CAUTI (<1.0%), CLABSI (0.1%), and hospital-onset MRSA BSI (0.1%) was low. SSI rate (7.8% overall) was higher in patients who developed pneumonia (18.4 vs 6.6, p = 0.004). MPI cultures grew gram-negative bacilli or S. aureus in 75%. The length of stay was longer in patients who developed a MPI than those who did not (17.4 vs 10.4 days, p < 0.0001). One-seventh of major head and neck flap surgeries were complicated by MPIs, three-quarters of infections developed within 1 week postoperatively. Gram-negative bacilli and S. aureus were the predominant pathogens.

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The utility of intra-oral ultrasound in improving deep margin clearance of oral tongue cancer resections

Mustafa G. Bulbul, Osama Tarabichi, Anuraag S. Parikh, Byung C. Yoon, Amy Juliano, Peter M. Sadow, William Faquin, Matthew Gropler, Ronald Walker, Sidharth V. Puram, Mark A. Varvares

Publication date 27-09-2021


To investigate the potential utility of intra-oral ultrasound (IOUS) in guiding deep margin clearance and measuring depth of invasion (DOI) of oral tongue carcinomas (OTC). Retrospective chart review of consecutive patients with T1-T3 OTC who underwent intraoperative ultrasound-guided resection and a comparator group that had undergone resection without the use of IOUS both by a single surgeon. Data was extracted from operative, pathology and radiology reports. Deep margins and DOI were reviewed by a dedicated head and neck pathologist. Correlation between histologic and ultrasound DOI was assessed using Pearson correlation. A total of 23 patients were included in the study cohort with a comparator group of 21 patients in the control group. None of the patients in the study cohort had a positive (cut-through) deep margin and the mean deep margin clearance was 8.5 ± 4.9 and 6.7 ± 3.8 for the IOUS and non-IOUS groups respectively (p-value 0.18) showing a non-significant improvement in the IOUS group. As a secondary outcome, there was a strong correlation between histologic and ultrasound DOI (0.9449). Ultrasound appears to be a potentially effective tool in guiding OTC resections. In this small series, IOUS facilitated deep margin clearance and resulted in a non-statistically significant increase in deep margin clearance. Intraoral ultrasound can accurately measure lesional DOI.

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Quality of life in patients with locally advanced head and neck cancer treated with concurrent chemoradiation with cisplatin and nimotuzumab versus cisplatin alone – Additional data from a phase 3 trial

Nandini Menon, Vijay Patil, Vanita Noronha, Amit Joshi, Atanu Bhattacharjee, Balajirao J Satam, Vijayalakshmi Mathrudev, Sarbani Ghosh Laskar, Kumar Prabhash

Publication date 25-09-2021


The addition of Nimotuzumab to radical chemoradiation (CRT) improved outcomes in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing radical CRT in a phase 3 randomized trial. The current study focuses on the quality of life (QoL) of patients in this trial. In this phase III randomized trial, patients with newly diagnosed, nonmetastatic, stage III/IV LAHNSCC of the oral cavity, oropharynx, hypopharynx, or larynx were randomized to receive cisplatin 30 mg/m 536 patients were randomized in this trial (268 in each arm) and 423 patients were included for QoL analysis. There was a significant change in the global health status QoL scores over time (p = 0.0016) with no difference between the two arms (p = 0.396). On longitudinal analysis there was a significant difference in the QoL scores in most of the function & symptom scales over time, but there was no significant difference in these scores between the two arms. QoL scores for most symptom scales worsened during treatment and improved thereafter in both arms. The addition of nimotuzumab to cisplatin based chemoradiation in LAHNSCC improved PFS, LRC and DFS without negatively impacting QoL.

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Do all patients with locoregionally advanced nasopharyngeal carcinoma benefit from the maintenance chemotherapy using S-1/capecitabine?

Man-yi Zhu, Xue-song Sun, Shan-shan Guo, Qiu-yan Chen, Lin-quan Tang, Li-ting Liu, Hai-qiang Mai

Publication date 22-09-2021


The goal of this study was to explore the benefits of S-1/capecitabine as maintenance therapy in locoregionally advanced nasopharyngeal carcinoma (NPC) patients with different risks of treatment failure. A total of 2205 eligible, locoregionally advanced NPC patients were recruited for this retrospective study. Multivariate Cox regression analysis was performed to identify optimal predictors of overall survival (OS) and distant metastasis-free survival (DMFS) for constructing the nomograms. Patients were stratified into high-risk or low-risk groups based on the total score of the nomograms. Propensity score matching (PSM) was performed to match the maintenance and non-maintenance cohorts in different risk groups. A log-rank test was performed to evaluate correlations between maintenance therapy and survival. A nomogram for OS was established (C-index, 0.664; 95% confidence interval, 0.635-0.693). The 5-year OS rate was significantly higher in the low-risk group than in the high-risk group (83.5% vs. 67.2%, P < 0.001). Patients in the high-risk group who received S-1/capecitabine maintenance therapy achieved significant improvement in the 5-year OS rate (82.8% vs. 67.1%, p = 0.034), whereas patients in the low-risk group did not (86.7% vs. 80.9%, P = 0.081). There was no significant difference in OS, DMFS, progression-free survival (PFS), or toxicities between the S-1 and capecitabine groups (all P > 0.05), and overall treatment-related adverse events (AEs) were not severe (grade 1-2). S-1/capecitabine maintenance therapy could prolong OS for locoregionally advanced NPC patients in the high-risk group. The toxicities of S-1/capecitabine maintenance therapy were mild and tolerable. Our findings can help guide maintenance therapy in locoregionally advanced NPC.

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Survival impact of increasing time to IMRT initiation following induction chemotherapy in nasopharyngeal carcinoma: A propensity score-matched analysis

Xin Zhou, Tingting Xu, Youqi Yang, Xing Xing, Chunying Shen, Chaosu Hu

Publication date 17-09-2021


To explore the prognostic impact of waiting time for radiotherapy (RT) after induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). A total of 648 NPC patients receiving IC between 2009 and 2011 were included Propensity score matching (PSM) was performed to balance the variables Survival outcomes were compared in subgroups based on time to RT (TTR) after IC. The optimal cutoff point for TTR was 28 days A total of 330 patients were selected by 1:2 PSM Stratified and dichotomized TTRs were both strongly correlated with prognosis Patients with TTR > 28 days had significantly worse 5-year LRFS, DMFS, DFS and OS than those with TTR ≤ 28 days (P < 0.05) In multivariate analysis, TTR > 28 days was an independent predictor of worse LRFS [HR = 2.08; 95% CI, 1.18-3.66; P = 0.011), DMFS (HR = 1.65; 95% CI, 1.04-2.62; P = 0.033), DFS (HR = 1.86; 95% CI, 1.35-2.62; P < 0.001) and OS (HR = 1.90; 95% CI, 1.26-2.85; P < 0.001) High-risk patients with T4 or N2-3 disease were highly susceptible to RT delay with impaired DFS and OS In high-risk patients with TTR > 28 days, concurrent chemotherapy yielded better DMFS (70.9% vs 52.0%, P = 0.041), DFS (52.5% vs 34.3%, P = 0.039) and OS (70.3% vs 53.2%, P = 0.048). Prolonged waiting is detrimental to survival in NPC, and it is strongly recommended to start RT within 28 days after IC T4/N2-3 NPC has a higher risk of treatment failure with delayed RT With potential protection against RT delay, concurrent chemotherapy should be performed in high-risk patients as salvage therapy.

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Multifocal regression and pathologic response predicts recurrence after neoadjuvant chemotherapy in head and neck squamous cell carcinoma

Kimberley L Kiong, Diana Bell, Christopher MKL Yao, Renata Ferrarotto, Carol M Lewis

Publication date 15-09-2021


Complete pathological response after neoadjuvant chemotherapy (NAC) in head and neck squamous cell carcinomas (HNSCC) is a good prognostic factor. Multifocal regression post-NAC in breast cancer has proven to impact locoregional control (LRC) but has not been evaluated in HNSCC. We evaluate the impact of multifocal regression and major pathologic response (MPR) on survival indices in HNSCC. Retrospective review of HNSCC patients receiving NAC followed by surgery with curative intent between March 2016 to March 2019 at MD Anderson Cancer Center. Tumor focality (uni- or multifocal), pathologic response and other pathologic data were collected. MPR was defined as ≤ 10% residual tumor. Overall survival (OS) and LRC were analyzed and multivariate Cox regression analysis was performed. 101 patients were analyzed, with 18.8% pathologic complete response, 18.8% with 1-10% viable tumor and 60.4% with > 10% viable tumor. 61 (60.4%) had unifocal disease while 19 (18.8%) had multifocal disease. Tumor focality was significantly associated with LRC but not OS, where the 3-year LRC was 82%, 69% and 52% (p = 0.015) for no viable tumor, unifocal disease and multifocal disease respectively. On multivariate analysis, multifocal disease (HR 10.43; 95 %CI 1.24-87.5) and extranodal extension (HR 4.4; 95 %CI 1.60-12.07) continued to be significant independent predictors of LRC. MPR group displayed significantly better 3-year OS (75% vs 51%, p = 0.041) and 3-year LRC (80% vs 62%, p = 0.011) than those with > 10% viable tumor. Multifocal regression and less than MPR after NAC in HNSCC predicts for locoregional recurrence and should be routinely reported.

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The impact of positive margin on survival in oral cavity squamous cell carcinoma

Vishaal Patel, Thomas J. Galloway, Jeffrey C. Liu

Publication date 12-09-2021


Positive margins are known to impact survival in oral cavity squamous cell carcinoma (OCSCC). We aimed to determine the impact of positive margins on survival and whether radiation improves survival following positive margins. Data was obtained from the National Cancer Database and included patients with cT1T2N0 OCSCC. Survival outcomes were assessed via log-rank test. Cox-regression analysis was performed to determine if positive margins or radiation, when applicable, correlated with survival after accounting for covariates. Positive margin patients had worse overall survival compared to negative margin control (HR = 1.76, p < 0.001) and reduced survival by 13%. On multivariate analysis, positive margins correlated with survival (HR = 1.60, p < 0.001). Radiation did not improve survival in positive margin patients (HR = 0.99, p = 0.55). Patients with positive margins have an 11-15% worse overall survival. Radiation does not appear to impact survival in patients with a positive margin.

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Association of specific single nucleotide variants (SNVs) in the promoter and 3′-Untranslated region of Vascular Endothelial growth factor (VEGF) gene with risk and higher tumour grade of head and neck cancers

Sadia Ajaz, Rabbia Muneer, Aisha Siddiqa, Muhammad Ali Memon, Sadaf Firasat, Aiysha Abid, Shagufta Khaliq

Publication date 12-09-2021


Head and Neck Cancers (HNCs)comprise one of the most frequent cancers in South-Asian region. Vascular Endothelial Growth Factor (VEGF) has a potent role in tumorigenesis and metastasis. Certain common single nucleotide variants (SNVs) in the highly polymorphic VEGF gene are correlated with variations in VEGF functions. The data for these SNVs in HNCs is scarce for South Asian populations. The present study addresses this shortfall. It investigates the association of two VEGF SNVs, -2578C/A (rs699947) in the promoter region and + 936C/T (rs3025039) in 3'-UTR, with the risk of HNCs and tumour characteristics. The study comprised 323 participants with 121 HNC patients and 202 controls. Germline DNA was isolated from peripheral blood samples. PCR-RFLP methods were optimized and validated by Sanger sequencing. After Hardy-Weinberg evaluation, the independent associations were analyzed under the assumptions of different genetic models. The χ VEGF -2578 A-allele, CA + AA, and AA genotypes had significant protective association against HNCs.
The respective ORs were: 0.651 (0.469-0.904), 0.613 (0.381 - 0.985), and 0.393 (0.193-0.804). VEGF + 936 T-allele, CT, and CT + TT genotypes had significantly increased susceptibility for HNCs. The respective ORs were 1.882 (1.001 - 3.536), 2.060 (1.035 - 4.102), and 2.023 (1.032 - 3.966). Additionally, VEGF + 936 CT and CT + TT genotypes showed significant associations with higher tumour grade (p-values < 0.029, and < 0.037, respectively). The present study is the foremost report of independent and unique associations of the investigated VEGF SNVs with HNCs.

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Tissue-resident memory T cells correlate with the inflammatory tumor microenvironment and improved prognosis in head and neck squamous cell carcinoma

Shota Ida, Hideyuki Takahashi, Reika Kawabata-Iwakawa, Ikko Mito, Hiroe Tada, Kazuaki Chikamatsu

Publication date 11-09-2021


Tumor-infiltrating T cell (TIL) is a major cell type involved in tumor eradication in the tumor microenvironment (TME). Among TILs, tissue-resident memory T cells (T We analyzed RNA-sequencing (RNA-seq) data obtained from The Cancer Genome Atlas (TCGA) database. Based on the gene expression of CD69 and CD4/CD8A, we identified T TCGA analysis revealed that T We highlighted the clinical and transcriptomic significance of T

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The prognostic value of radiologic extranodal extension in nasopharyngeal carcinoma: Systematic review and meta-analysis

Tsung-You Tsai, Yung-Chih Chou, Yi-An Lu, Chung-Jan Kang, Shiang-Fu Huang, Chun-Ta Liao, Kai-Ping Chang

Publication date 11-09-2021


The prognostic value of radiologic extranodal extension (rENE) in nasopharyngeal carcinoma remains controversial. In this study, a meta-analysis was performed to assess the prognostic value of ungraded rENE and unambiguous advanced rENE. A literature search through Pub Med, Cochrane Library, EMBASE and manual searches was conducted until May 2021. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival and distant metastasis-free survival were extracted and pooled. Nine eligible studies were published between 2012 and 2021. The pooled patient number was 7532 (range 61-1887). Seven studies were eligible for the analysis of ungraded rENE, while 3 studies were eligible for unambiguous advanced rENE. The results showed that ungraded rENE was associated with worse overall survival (HR 1.85, 95% CI 1.04-3.27) and significantly associated with worse distant metastasis-free survival (HR 2.07, 95% CI 1.36-3.13). On the other hand, unambiguous advanced rENE was significantly associated with worse overall survival (HR 2.62, 95% CI 2.12-3.25) and worse distant metastasis-free survival (HR 3.14, 95% CI 1.85-5.33). In nasopharyngeal carcinoma, both ungraded and unambiguous advanced rENE are significant prognosticators of overall survival and distant metastasis-free survival. More prospective studies are required to determine its role in risk stratification or clinical staging.

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Metachronous second primary neoplasia in oropharyngeal cancer patients: Impact of tumor HPV status. A GETTEC multicentric study

Florent Milliet, Alexandre Bozec, Renaud Schiappa, Julien Viotti, Anouchka Modesto, Olivier Dassonville, Gilles Poissonnet, Bruno Guelfucci, Alain Bizeau, Sebastien Vergez, Agnes Dupret-Bories, Renaud Garrel, Nicolas Fakhry, Laure Santini, Benjamin Lallemant, Guillaume Chambon, Anne Sudaka, Frederic Peyrade, Esma Saada-Bouzid, Karen Benezery

Publication date 10-09-2021


Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis. Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

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Effect of elective neck dissection versus sentinel lymph node biopsy on shoulder morbidity and health-related quality of life in patients with oral cavity cancer: A longitudinal comparative cohort study

Gerben van Hinte, Tolunay Sancak, Willem L.J. Weijs, Matthias A.W. Merkx, Ruud A. Leijendekkers, Maria W.G. Nijhuis-van der Sanden, Robert Takes, Caroline M. Speksnijder

Publication date 08-09-2021


To research the difference in shoulder morbidity and health-related quality of life between patients with cT A longitudinal study with measurements before surgery, 6 weeks, 6 months, and 12 months after surgery. Shoulder morbidity were determined with measurements of active range of motion of the shoulder and patient-reported outcomes for shoulder morbidity (SDQ, SPADI) and health-related quality of life (HR-QoL) (EQ5D, EORTC-QLQ-HN35). Linear mixed model analyses were used to analyze differences over time between patients that had END, SLNB or SLNB followed by complementing neck dissection. We included 69 patients. Thirty-three patients were treated with END. Twenty-seven patients had SLNB without complementing neck dissection (SLNB), and nine were diagnosed lymph node positive followed by completion neck dissection (SLNB + ND). Ipsilateral shoulder abduction (P = .031) and forward flexion (P = .039) were significantly better for the SLNB group at 6 weeks post-intervention compared to the END and SLNB + ND group. No significant differences for shoulder morbidity, or health-related quality of life were found at 6 weeks, 6 months, and 12 months between the three groups. With oncologic equivalence for the END and SLNB as strategies for the cN

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Diagnostic value of indocyanine green for sentinel lymph node mapping and lymph node metastasis in oral/oropharyngeal carcinoma

Nan Lin, Jinsheng Gao, Hang Wang, Hao Zhang, Yu Xiang, Xuelei Ma

Publication date 17-10-2021


Indocyanine green (ICG) fluorescence-based sentinel lymph node (SLN) biopsy has been promoted to detect early metastasis of oral/oropharyngeal carcinoma, but its diagnostic value still remains unclear. In this letter, we identified 6 studies on ICG fluorescence based SLN in the detection of lymph node metastasis in oral/oropharyngeal carcinoma. For detection of metastatic lymph node, the overall sensitivity and specificity of the studies were 0.86 and 0.91, respectively. SROC curve was determined according to the combined sensitivity and specificity, and the overall area under the curve AUC was 0.93. On the whole, ICG fluorescence-based SLN biopsy showed promising effect for earlier detection and staging.

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Prevalence of occult level 2b nodal metastases in cN0 squamous cell carcinoma of the oral cavity: A systematic review and meta-analysis

Fabio Ferreli, Bianca Maria Festa, Andrea Costantino, Luca Malvezzi, Giovanni Colombo, Giuseppe Spriano, Giuseppe Mercante, Armando De Virgilio

Publication date 02-10-2021


Elective neck dissection of levels I, II and III is being increasingly used for detecting occult node metastases in patients with oral squamous cell carcinoma (OSCC) and clinically negative neck (cN0). The most frequent potential long-term complication of this procedure is shoulder dysfunction, because of micro- or macroscopic damage to the spinal accessory nerve (SAN). In particular, many studies have reported an association between SAN damage and dissection of level 2b. Furthermore, level 2b dissection is a technically demanding and time-consuming procedure. Our study aims to clarify whether level 2b sparing in cN0 patients with OSCC can be oncologically justifiable. The Pub Med, Cochrane and Scopus databases were searched by three different authors for articles on this topic. The primary endpoint of the meta-analysis was the overall prevalence of occult metastases in cervical level 2b nodes in patients with OSCC and clinically negative neck. The meta-analysis was performed using R version 4.0.1. A total of 13 studies and 937 patients were included. The cumulative rate of occult nodal metastases in level 2b was 0.8% (n = 937, 95% CI: 0.1% - 2.2%, τ

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Intraoral ultrasonography A high precision route map for achieving “clear” margins in squamous carcinomas of oral tongue!

Kondamudi Dheeraj, Suresh Mani, Rajeev Kumar

Publication date 23-04-2021


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Patient specific follow-up to monitor the risk of malignant transformation on oral mucosa

N. Ezgi Ozer, Betul Ilhan, Pelin Guneri

Publication date 26-04-2021


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A rare case of Kimura disease with lumps on the cheek and behind the ear

Jia-ling Chen, Qian Wang, Liang-mei Huang, Yong-hui Xu, Dan-dan Dong, Yu-feng Lin, Rong-yi Chen, Jian-qiang Shi

Publication date 03-05-2021


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Implementation of human papillomavirus circulating tumor DNA to identify recurrence during treatment de-escalation

Catherine T. Haring, Collin Brummel, Chandan Bhambhani, Brittany Jewell, Molly Heft Neal, Apurva Bhangale, Keith Casper, Kelly Malloy, Scott McLean, Andrew Shuman, Chaz Stucken, Andrew Rosko, Mark Prince, Carol Bradford, Avraham Eisbruch, Michelle Mierzwa, Muneesh Tewari, Francis P. Worden, Paul L. Swiecicki, Matthew E. Spector

Publication date 19-06-2021


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Central mucoepidermoid carcinoma associated with impacted tooth mimicking as dentigerous cyst

Kedar Vaidya, Gargi S. Sarode, Namrata Sengupta, Sachin C. Sarode, Kiran Gadre, Pushkar Gadre, Shankargouda Patil

Publication date 17-06-2021


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A comparative study on using superior thyroid artery perforator flaps versus traditional sternocleidomastoid myocutaneous flaps for reconstructions after oral cancer ablation: “New tricks for old dogs”?

Chunyue Ma, Surui Sheng, Yi Shen, Weijin Gao, Thorsen Haugen, Liang Wang, Jian Sun

Publication date 16-06-2021


To introduce new superior thyroid artery perforator flaps (STAPF), and to compare the clinical outcomes with sternocleidomastoid myocutaneous flaps (SCMMF) for their intraoral applications. Between January 2013 and December 2020, forty-three oral cancer patients who received post-oncologic reconstructions with one of these two regional flaps were retrospectively collected. Their techniques and outcomes were compared. All the STAPFs were preprepared with radiologic evaluations. Despite the common arterial origins, the compositions and harvesting procedures of STAPF and SCMMF were different. Though SCMMFs (n = 23) were designed in rotational styles, most STAPFs (n = 20) were septocutaneous perforator flaps, with 2 chimeric ones. In addition, the sizes of STAPFs were generally larger than those of SCMMFs (p = 0.006). Success rate for STAPFs was much higher, with only three partial cutaneous necroses. Radiotherapy delay was more frequently found in those reconstructed with SCMMFs (P = 0.046), mostly due to fistula formations. Besides, incomplete level IIB dissections were also reported in 9 (20.9%) patients in SCMMF group. In our study, the overall survival was affected by both flap conditions (p = 0.014, 1.333-12.881) and postoperative surgical complications (except fistula) (P = 0.005, 2.240-84.134). Functionally speaking, post-reconstructive speech and neck mobility (p < 0.001) were better in the STAPF group. With accumulated experiences on the use of locoregional flaps in the neck, STAPF, when well-prepared, can provide superior reconstructive outcomes for various intraoral defects. As a comparison with SCMMF in the same middle region, STAPF is a viable option with higher success rates and oncological safety for oral cancer patients.

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Linking chronic periodontitis and oral cancer: A review

Avinash Kavarthapu, Kaarthikeyan Gurumoorthy

Publication date 19-06-2021


The aim of this article is to survey the accessible writing on the pathogenetic systems engaged with the relationship between oral malignancy and periodontitis. Gingival tissue contains multiple microbiota, which can induce inflammatory reactions. This reaction plays a crucial role in assessing the susceptibility of patients to periodontal diseases. The link between chronic periodontitis and the risk of malignancy through this inflammation of the affected epithelium have been studied thoroughly. Many studies have reported that, chronic periodontitis has systemic influence which has high risk of developing different types of cancers. Also, various confounding factors such as consumption of alcohol, smoking, diet, age and gender have been found to be associated with both chronic periodontitis and oral cancer. An online quest for a wide range of articles distributed was started utilizing MEDLINE/Pub Med, with the keywords, for example, 'oral squamous cell carcinoma (OSCC)', 'oral microbiota,' 'microorganisms and malignancy and Porphyromonas gingivalis. This review aimed to study the current literature linking chronic periodontitis and oral cancer.

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New nodules in oral cavity and forehead face: A decisive clinical clue to the diagnosis of epithelioid sarcoma

Yan-li Wang, Yan Zhu, Shu-xian Jin

Publication date 17-06-2021


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Versatility of a single piece scapular tip and lateral border free flap for mandibular reconstruction: A virtual study on angle correspondence

Khanh Linh Tran, Edward Wang, Sidney Fels, Antony Hodgson, Eitan Prisman

Publication date 19-06-2021


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Hybrid oral potentially malignant disorder: A neglected fact in oral submucous fibrosis

Sachin C Sarode, Shailesh Gondivkar, Gargi S. Sarode, Amol Gadbail, Monal Yuwanati

Publication date 21-06-2021


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p16 positive oropharyngeal small cell cancer: A case report

Nada Al Masalmeh, Geetika Kukreja, Feras Zaiem, S. Naweed Raza, Harold Kim, Misako Nagasaka, Ammar Sukari

Publication date 01-07-2021


Extra-pulmonary small cell carcinomas (EPSCC) are rare malignancies. Like small cell lung cancer (SCLC), they are aggressive malignancies with dismal prognosis. We here report a case of a middle-aged man who presented with odynophagia and cervical lymphadenopathy. Diagnostic workup confirmed the diagnosis of locally-advanced p16-positive oropharyngeal cancer (OPC) with a surprising histology of small cell cancer, suggesting a human papilloma virus (HPV)-related oropharyngeal cancer with small cell differentiation. HPV oropharynx infection is a well-known risk factor for squamous cell carcinoma of the oropharynx, but it is unknown if it may increase the risk of other OPC histology.

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Caution with carotids: A necessary cognizance

Adarsh Kudva, Vasantha Dhara, BR Patil, Mridula Sankaran

Publication date 26-06-2021


Most aberrations in the cervical course of the internal carotid artery are generally encountered as incidental findings due to their asymptomatic nature. However these morphological variations if not identified intra operatively or pre operatively may lead to vascular accidents. It is essential to be aware of the existence of tortuosity, kinking, and coiling of these great vessels while considering patients for surgeries of head and neck cancer, pharyngeal resections, traumatic injury repair, etc. Our paper presents a case series of four patients in whom carotid dolichoarteriopathies were observed during the course of neck dissection. It aims to highlight the precautions required to avoid morbidity in such patients.

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Clinical and treatment course of lung carcinoma from adult-onset recurrent respiratory papillomatosis with lung involvement: A case report

Marcelo Cardoso Figueiredo, Mariana Chantre-Justino, Rafael Latini Ruback, Paulo Pires de Mello, Gilda Alves, Maria Helena Ornellas

Publication date 26-06-2021


Neoplasms induced by human papillomavirus (HPV) infection are generally associated to high-risk HPV types. Recurrent respiratory papillomatosis (RRP) is a rare and chronic HPV-related disease characterized by papillomatous lesions in the respiratory tract, usually affecting larynx. RRP rarely comprises malignant transformation since the low-risk HPV-6 and/or HPV-11 are the most commonly found in the disease. We described a case of one adult-onset RRP (29-year-old, female) with HPV-6 infection affecting vocal folds and extra-laryngeal sites. Computed tomographic scan of the chest revealed papillomatosis with pulmonary spread showing multiple nodules and cavities. Lung involvement later progressed to squamous cell carcinoma of the lung. Patient's pregnancy during investigations may have accelerated lung carcinoma development due to immunological changes. Immunohistochemistry revealed PD-L1 high expression in tumor biopsy and, after pregnancy, the oncology treatment included a combination of pembrolizumab (PD-L1 inhibitor) to chemotherapy and also radiotherapy, showing considerable results. Patient died due to lung cancer complications 15 months after cancer diagnosis. RRP management associated with lung involvement and poor prognostic outcome, such as lung carcinoma, is still a big challenge. In this report, we described the clinical and treatment course of RRP progression to highlight the need for attention to future patients.

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P16-positive secondary tongue squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: A case report and literature review

Tiantian Wu, Zhenmin Liu, Xiangzhi Yong, Guocheng Mei, Qiaozhi Jiang, Meifei Fang, Ping Li, Zhongming Zhang, Renchuan Tao

Publication date 05-07-2021


As a method to improve the survival rate of patients with hematological malignancies, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increasingly been used for treatment. However, some potentially serious complications after allo-HSCT, including graft-versus-host disease, graft failure, infection, end-organ toxicity, and secondary malignancies, will determine the success of hematopoietic reconstitution. Here, we describe a case of a patient with p16-positive tongue squamous cell carcinoma (TSCC) following allo-HSCT. A 62-year-old man who had previously received allo-HSCT due to acute lymphocytic leukemia (AML) presented with erosions on the back of the tongue surrounded by multiple white patches, which were compatible with oral chronic graft-versus-host disease (cGVHD). During follow-up, a circular-like erosive lesion appeared on the right dorsal surface of the tongue. Biopsy of this lesion confirmed early invasive TSCC (T2N0M0). Partial glossectomy and tongue reconstruction were performed after cessation of immunosuppressants. Immunohistochemical (IHC) staining was positive for p16 and ki-67, suggesting a probable active human papillomavirus (HPV) infection. Six months after surgery, the patient showed no signs of metastasis or recurrence nor progression of oral GVHD.

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Is cellularity alone sufficient to sub-grade malignant melanoma histologically as spindle cell/desmoplastic variant?

Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, Casilda L. Sushanthi, Abilasha Ramasubramanian

Publication date 22-08-2021


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Multifaceted multinucleated giant cells in oral squamous cell carcinoma

Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, K. Monica

Publication date 26-06-2021


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The characteristics and prospects of reflectance confocal microscopy for noninvasive diagnosis of oral potentially malignant disorders

Wei Liu, Xi Yang, Zhengyu Shen, Linjun Shi

Publication date 16-08-2021


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Definitive tumor directed therapy confers a survival advantage for metachronous oligometastatic HPV-associated oropharyngeal cancer following trans-oral robotic surgery

Christopher M. Wright, Daniel Y. Lee, David Shimunov, Ruben Carmona, Andrew R. Barsky, Lova Sun, Roger B. Cohen, Joshua M. Bauml, Robert M. Brody, Devraj Basu, Christopher H. Rassekh, Ara A. Chalian, Jason G. Newman, Karthik Rajasekaran, Gregory S. Weinstein, John N. Lukens, Alexander Lin, Samuel Swisher-McClure

Publication date 03-09-2021


To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy. This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]. Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004). In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.

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Associations between testosterone and patient reported sexual outcomes among male and female head and neck cancer patients before and six months after treatment: A pilot study

Irma M. Verdonck-de Leeuw, Heleen Melissant, Birgit I. Lissenberg-Witte, Robert J. Baatenburg de Jong, Martin den Heijer, Johannes A. Langendijk, C. René Leemans, Johannes H. Smit, Robert P. Takes, Chris H.J. Terhaard, Femke Jansen, Ellen Laan

Publication date 31-08-2021


To investigate associations between testosterone and patient reported sexual problems and need for sexual care in head and neck cancer patients at time of diagnosis and 6 months after treatment. Data and samples were used of 40 patients (20 men, 20 women) before and 6 months after treatment. Outcome measures were total testosterone level (TT) and free testosterone index (FTI), testosterone insufficiency (TI), the EORTC QLQ-HN35 Sexuality subscale, the subscales of the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), and the Sexuality subscale of the Short-Form Supportive Care Needs Survey (SCNS-SF34). In men, higher FTI before treatment was significantly associated with better IIEF Orgasm (p = 0.020) and at 6 months follow-up with IIEF Desire (p = 0.019). Before treatment, insufficient testosterone was present in 5 males (25%) and in 3 at follow-up (15%) (2 patients who had TI before treatment plus one). In women, higher TT at follow-up was significantly associated with better EORTC Sexuality (p = 0.031) and FSFI Satisfaction (p = 0.020); FTI at follow-up was associated with FSFI Satisfaction (p = 0.012). Before treatment, TI was present in 2 women (10%) and in 3 (15%) at follow-up (the same 2 patients plus one). This pilot study showed that testosterone seems to be associated with patient reported sexual outcomes among male and female head and neck cancer patients. It is estimated that 10-25% of HNC patients may have testosterone insufficiency before treatment and/or at 6 months after treatment.

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Surgical and oncological outcomes of transoral robotic total laryngectomy: A case series

Stéphane Hans, Emilien Chebib, Younès Chekkoury-Idrissi, Léa Distinguin, Marta Circiu, Grégoire Vialatte de Pemille, Aude Julien-Laferriere, Lise Crevier-Buchman, Jérôme R. Lechien

Publication date 03-09-2021


To evaluate the oncological, functional and voice rehabilitation outcomes of transoral robotic surgery for total laryngectomy (TORS-TL). A retrospective chart review of patients treated by TORS-TL was conducted at a single academic medical center.
The following outcomes were studied: indication; average robotic set-up and operative times; mean estimated blood loss; postoperative complications; re-feeding features; mean hospital stay; need of adjuvant therapy and voice rehabilitation type. TORS-TL was performed in 10 patients for the following indications: nonfunctional larynx (N = 2); low-grade cricoid chondrosarcoma (N = 3) and recurrent laryngeal cancer after (chemo) radiation (N = 5). Two patients were excluded because the larynx was not exposable. Average robotic set-up and operative times were 20 and 278 min, respectively. The mean estimated blood loss was 50 mL. The mean hospital stay was 13.9 days (8-28 days). There was no local recurrence in patients operated for cancer recurrence (N = 5) 5 years after the surgery. Distant metastases occurred in one patient. A patient with laryngeal chondrosarcoma experienced local failure 3 years after TORS-TL. The voice rehabilitation consisted of esophageal voice (N = 2) and tracheoesophageal prosthesis (Provox®, N = 8). The main reasons for prosthesis replacement were transprosthetic (79%) and periprosthetic leaks (21%). The median lifespan of prostheses was 81 days. TORS-TL may be a safe and effective surgical approach for selected surgical indications. Future controlled studies are needed to determine additional indications and limitations of this procedure.

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Development and validation of a population-based model for predicting the regional lymph node metastasis in adolescent differentiated thyroid carcinoma

Yu Min, Ke Xiang, Yang Feng, Hang Chen, Jialin Chen, Xiaoyuan Wei, Guobing Yin

Publication date 28-08-2021


Adolescent differentiated thyroid carcinoma (DTC) is a rare type of thyroid cancer that represents a special entity of all endocrine-related cancer. This study aims to establish the first nomogram for predicting the regional (central and lateral) lymph node metastasis (LNM) in the adolescent population for better surgical management. We retrospectively reviewed the clinicopathology characteristics of adolescent patients with DTC in the Surveillance, Epidemiology, and End Results database between 2010 and 2015. A total of 1,930 adolescent patients between the ages of 10 and 24 years from the SEER database were enrolled in this study. Six predictive factors including age, race, histology, multifocality, extrathyroidal invasion (EI) and tumor size were identified to be significantly associated with the regional LNM via univariate and multivariate logistic regression analyses. These indicators were used to construct a nomogram for predicting the regional LNM in adolescent patients with DTC. Moreover, a satisfied predictive ability of the model was determined with a C-index of 0.794, supported by an internal validation group with a C-index of 0.776. The Decision Curve Analysis and calibration curve further conducted a great agreement in our model. The first predictive model containing multiple factors has been successfully established with good discrimination for predicting the regional LNM in adolescent patients with DTC. This nomogram could effectively help surgeons to make better individualized surgical decision intraoperatively, especially in terms of whether cervical lymph node dissection (LND) is warranted.

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Delayed diagnosis of palatal adenoid cystic carcinoma: Review of diagnostic workup and image features of perineural spread

Peggy P. Lee, Griffin C. Guess, Austin E. Schumacher, Roberta W. Dalley

Publication date 27-08-2021


Adenoid cystic carcinoma (ACC) is the malignancy most likely to spread perineurally. Delayed diagnosis often leads to undetected perineural spread (PNS). Better understanding of diagnostic processes, clinical and imaging features in ACC may allow earlier diagnoses. A retrospective records search of the University of Washington Radiology archive identified patients with palatal ACC diagnosis and pre-treatment MDCT and/or MRI. Demographic data, clinical findings, diagnostic workup history and image features including the presence of PNS were recorded. 44 patients met inclusion and exclusion criteria. Symptoms included pain, mass, numbness, and sinonasal congestion. The most common finding on clinical examination was visible or palpable palatal mass. 55% of patients were evaluated by a dentist pre-diagnosis. Most common initial impressions were infection and/or dental disease. PNS was identified in 81.8% of patients, most commonly at pterygopalatine fossa, palatine foramina/canals, Vidian canal, or foramen rotundum. PNS was statistically significantly associated with paresthesia (p = 0.003) but not with tumor size, age, gender, or tobacco history. 44% of patients were diagnosed ≥1 year from initial symptoms, with a mean delay of 18.3 (range < 1-72) months. This study represents the first analysis of the nature of the diagnostic process of palatal ACC. Majorities of patients were evaluated by a general dentist pre-diagnosis. PNS was identified in a majority of patients and all the patients who presented with paresthesia had evidence of PNS. Despite patients presenting with paresthesia, palatal ACC is often initially misdiagnosed resulting in delayed diagnosis.

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Identification of patients for a delayed extubation strategy versus elective tracheostomy for postoperative airway management in major oral cancer surgery: A prospective observational study in seven hundred and twenty patients

Sheila Nainan Myatra, Sushan Gupta, Anil K. DCruz, Vithal Rajanala, Harsh Dhar, Shilpi Sharma, Jigeeshu Vasishtha Divatia

Publication date 28-08-2021


Tracheostomy (TT) and delayed extubation (DE) are two approaches to postoperative airway management in patients after major oral cancer surgery. We planned a study to determine the safety of overnight intubation followed by extubation the next morning (DE) compared to elective TT and to identify factors that were associated with a safe DE (maintenance of a patent airway). We conducted a prospective observational study in a tertiary referral cancer care center. We included adult patients undergoing elective major oral cancer surgery under general anesthesia with tracheal intubation. The decision regarding postoperative airway management using either TT or DE was made according to the usual practice at our center. We screened a total of 4477 patients, 720 patients were included. DE was performed in 417 patients (58.4%) and TT in 303 patients (42.4%). On multivariable analysis, T1-T2 tumor stage, absence of extensive resection, primary closure or reconstruction using fasciocutaneous flap, absence of preoperative radiation, no neck dissection or unilateral neck dissection and shorter duration of anesthesia were independent predictors for a safe DE. Overall complications (4.3% versus 22.5%, p = 0.00) and airway complications (1.7% versus 8.7%, p = 0.00) were lower in the DE compared to the TT group respectively. DE was associated with a shorter hospital stay (7.2 ± 3.7 versus 11.5 ± 7.2 days, p = 0.00), time to oral intake and speech compared to TT. A DE strategy after major oral cancer surgery is a safe alternative to TT in a select group of patients.

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Right colonic interposition for severe pharyngoesophageal stricture in head and neck patients: A feasible rescue strategy after multiple failed reconstructive options

C Carnevale, A Pagán-Pomar, A Bianchi, P Sarría-Echegaray, C Morales-Olavarría, G Til-Pérez

Publication date 06-09-2021


Severe pharyngeal stricture is an uncommon complication that may occur afer laryngectomy especially in irradiated patients. Its management is a challenge and high risk of recurrence after reconstruction exists. We present two patients with severe end-stage pharyngoesophageal stricture after several failed attempts of reconstruction with regional and free flaps, in which a right colon transposition was performed. Twenty days after surgery both patients were able to tolerate an oral diet, and no minor or major complications were observed. Right colonic transposition may be a valid option for secondary pharyngeal reconstruction if other less invasive methods such as regional or free flaps have failed to restore the pharyngoesophageal continuity or if the inferior location of stricture makes a tension free anastomosis impossible.

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The impact of induction chemotherapy on long-term quality of life in patients with locoregionally advanced nasopharyngeal carcinoma: Outcomes from a randomised phase 3 trial

Qi Yang, Le Xia, Mei Lin, Meng-Xia Zhang, Chong-Yang Duan, You-Ping Liu, Yu-Long Xie, Zhi-Qiang Wang, Rui You, Xiong Zou, Yi-Jun Hua, Pei-Yu Huang, Rui Sun, Ming-Huang Hong, Ming-Yuan Chen

Publication date 24-08-2021


Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

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Survival analysis of patients with advanced hypopharyngeal cancer comparing patients who received primary surgery to those who received chemoradiation: An analysis of the NCDB

Colleen G. Hochfelder, Vikas Mehta, Rafi Kabarriti, Aileen P. McGinn, Enrico Castellucci, Thomas J. Ow

Publication date 22-08-2021


The objective of this study was to use the American College of Surgeons' National Cancer Database (NCDB) to examine the association between primary treatment and overall survival (OS) among patients with locoregionally advanced hypopharyngeal cancer. 6,055 adult patients diagnosed between 2004 and 2015 with stage III or IV, M0, hypopharyngeal squamous cell carcinoma were identified within the NCDB. Patients who received primary chemoradiation (CRT) were compared to those that received surgery with adjuvant radiation or chemoradiation (S + Adj). OS was compared between treatment groups using Kaplan-Meier analyses, propensity score adjustment, and Cox regression analyses. The median survival was 22.7 months (IQR 11.0-49.0). The S + Adj group had a significantly higher comorbidity score, higher grade disease, and more advanced stage disease than the CRT group. S + Adj was associated with significantly improved survival when compared to CRT (p < 0.0001). A propensity score adjusting for facility type, facility location, care at multiple facilities, histology, and T stage was developed. S + Adj was associated with longer survival (HR: 0.72, 95% CI: 0.64-0.80) when compared to CRT in a multivariable Cox regression analysis (adjusting for age, race and ethnicity, insurance status, a comorbidity index, diagnosis year, treatment delay, N stage, and the propensity score). S + Adj was associated with significantly improved survival among those with T2 disease (p = 0.02), T3 disease (p = 0.02), and T4 disease (p < 0.0001) in sensitivity analyses examining these subcohorts independently. Among patients with advanced hypopharyngeal cancer reported in NCDB, treatment with S + Adj was associated with longer survival compared to those treated with primary CRT.

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Impact of sarcopenia in locally advanced head and neck cancer treated with chemoradiation: An Indian tertiary care hospital experience

Puneet Nagpal, Deep S. Pruthi, Manish Pandey, Ashu Yadav, Harpreet Singh

Publication date 18-08-2021


Sarcopenia is emerging as a poor prognostic factor in terms of treatment outcome as well as complications in cancer patients. This study aims to determine the prevalence of sarcopenia and its impact on outcome and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemo radiotherapy. Three hundred patients of locally advanced HNSCC were included. All patients were treated with radical radiotherapy dose of 70 Gy/35# over 7 weeks along with concurrent chemotherapy. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscle mass at level C3. The impact of sarcopenia on treatment outcome, Disease Free Survival (DFS) and toxicity was evaluated. Association between patient factors and outcome was calculated in univariate and multivariate analyses. Sarcopenic patients were more likely to be elderly, female gender and hypopharyngeal primary. The average SMI of the entire patient cohort was 31.9 cm Sarcopenia in HNSCC patients receiving definitive chemo radiotherapy is an independent prognostic factor and is associated with a worse treatment outcome and more toxicities.

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Prognostic impact and potential predictive role of baseline circulating tumor cells in locally advanced head and neck squamous cell carcinoma

Thiago Bueno de Oliveira, Alexcia Camila Braun, Ulisses Ribaldo Nicolau, Emne Ali Abdallah, Vanessa da Silva Alves, Victor Hugo Fonseca de Jesus, Vinicius Fernando Calsavara, Luiz Paulo Kowaslki, Ludmilla T. Domingos Chinen

Publication date 18-08-2021


The prognostic impact of circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is yet to be determined, with conflicting results in previous trials. The role of induction chemotherapy (ICT) in the management of LA-HNSCC is controversial with no predictive biomarkers to guide treatment strategy in this scenario. The aim of this trial is to determine the prognostic impact of CTCs and CTM, their biomarkers expression by immunocytochemistry (ICC), and its potential role as predictors of ICT benefit in LA-HNSCC. Prospective study, with newly diagnosed stage III/IV non-metastatic LA-HNSCC patients treated with curative intent. Blood samples analyzed for CTCs and CTM before treatment using the ISET method. A total of 83 patients were included. CTCs counts were an independent prognostic factor for overall survival (OS; HR: 1.17; 95 %CI: 1.05-1.31; p = 0.005) and progression free survival (PFS; HR:1.14; 95 %CI: 1.03-1.26; p = 0.007). Using the Lausen and Schumacher technique, 2.8 CTCs/mL for OS and 3.8 CTCs/mL for PFS were defined as the best cut-offs. CTM were detected in 27.7% of patients, correlating with worse PFS (HR = 2.70; IC95%: 1.30-5.58; p = 0.007). MRP-7 expression in CTM correlated with worse OS (HR = 3.49; 95 %CI: 1.01-12.04; p = 0.047) and PFS (HR = 3.62; 95 %CI: 1.08-12.13; p = 0.037). CTCs counts were predictive of complete response to treatment (OR = 0.74; 95 %CI: 0.58-0.95; p = 0.022) and high counts (cut-off 3.8/mL) and CTM were potential predictors of ICT benefit. CTCs/CTM had significant prognostic impact and potential role as predictors of ICT benefit in LA-HNSCC.

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Accuracy of autofluorescence and chemiluminescence in the diagnosis of oral Dysplasia and Carcinoma: A systematic review and Meta-analysis

Antonio Moffa, Lucrezia Giorgi, Andrea Costantino, Luigi De Benedetto, Michele Cassano, Giuseppe Spriano, Giuseppe Mercante, Armando De Virgilio, Manuele Casale

Publication date 17-08-2021


To define the accuracy of autofluorescence-based (AF) and chemiluminescence-based (CL) systems in the diagnosis of oral dysplastic and malignant lesions in addition to the Conventional Oral Examination (COE). The study was performed according to the PRISMA-DTA guidelines. A total of 2631 oral cavity lesions (AF, n = 2076; CL, n = 555) from 26 studies (AF = 17; CL = 9) was used for calculation of diagnostic accuracy parameters. The overall pooled sensitivity and specificity of the AF were 81.3% (95% CI: 74.3% - 87.5%) and 52.1% (95% CI: 36.9% - 67.1%), respectively. Cumulative diagnostic odds ratio (DOR) was 5.44 (95% CI: 2.29 - 10.56) with a significant heterogeneity between studies (I AF and CL present a high sensitivity in the diagnosis of dysplastic and malignant oral cavity lesions, demonstrating that diagnostic biopsies may be avoided in case of a negative test result. Both tests have a low specificity, and the reduction of the false positive rate compared to the COE alone remains poor.

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Regular clinical follow-up of oral potentially malignant disorders results in improved survival for patients who develop oral cancer

Fredrik Jäwert, Jennie Nyman, Emma Olsson, Claudia Adok, Madeleine Helmersson, Jenny Öhman

Publication date 10-08-2021


To evaluate whether clinical follow-up programs of oral potentially malignant disorders (OPMD) result in earlier detection and improved survival rates if malignant transformation occurs, as compared to OPMD patients without follow-up and other patients with oral squamous cell carcinoma (OSCC). Three OSCC groups were retrospectively studied for disease stage at diagnosis and survival rates (N = 739): Group A, patients with OSCC with regular follow-up of preceding OPMD (N = 94); Group B, patients with OSCC with preceding OPMD but no follow-up (N = 68); Group C, patients with OSCC without previously known OPMD diagnosis (N = 577). The patients with OPMD with follow-up (Group A) was diagnosed at a significantly earlier stage and have significantly higher survival rates compared to Group B (p < 0.001 and p = 0.022, respectively) and Group C (p < 0.001 and p < 0.001, respectively). There was no significant difference between Group B and Group C in terms of survival rate (p = 0.143) or stage at diagnosis (p = 0.475). Patients with OPMD and follow-up (Group A) had a 5-year net survival rate of 90.0% (95%CI 80.3-100.8%), as compared to 68.3% percent (95% CI 54.5-85.7) for Group B and 56.1% (95% CI 51.4-61.3) for Group C. The results of this study indicate that regular follow-up of patients with OPMD results in earlier detection of OSCC (if malignant transformation occurs) and improved survival.

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Genomic landscape and tumor mutation burden analysis of Chinese patients with sarcomatoid carcinoma of the head and neck

Hai-bing Chen, Xiao-yang Gong, Wang Li, Dong-sheng Chen, Le-le Zhao, Si Li, Ming-zhe Xiao, Lei Cheng, Xi Chen

Publication date 10-08-2021


Sarcomatoid carcinoma (SC) of the head and neck (HN) is a rare disease that has both sarcomatoid and cancerous components. The genetic background and mechanisms of tumorigenesis remain largely unrevealed, and the progress of precision therapy has been limited. Targeted DNA-based next-generation sequencing (NGS) was performed by a 539 genes panel of pan-cancer in 12 patients with SC of the HN to identify their genetic alterations and investigate clinically actionable mutations for use in precision treatment. TP53 was identified as the most frequently mutated gene. Genes related to the cell cycling, chromatin remodeling and histone modification were found to be frequently mutated in patients with SC of the HN. Alterations in receptor tyrosine kinases (RTKs) were also found in six patients. In addition, four patients had mutations in members of the downstream RAS and PI3-kinase pathways, PIK3CA was identified as the most frequently mutated gene in this pathway. The tumor mutation burden (TMB) value ranged from 0.71 to 14.71 per megabase, with a median of 4.34. The TMB value of PIK3CA mutation patients was significantly higher than that of PIK3CA wild-type patients. This was the first study to investigate genomic alterations specifically in Chinese patients with SC of the HN. Our research results showed that 10 out of 12 patients can match the targeted therapies or immunotherapy currently available in clinical practice or active clinical trials, suggesting precision therapy has the potential utility to improve the long-term prognosis for patients with the rare disease. Due to the small number of patients in this study, the findings need to be validated in a larger cohort.

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Serum selenium predicts achievement of full-dose cisplatin in concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: A prospective, observational study

Akira Ohkoshi, Ryo Ishii, Shun Wakamori, Yuki Nakayama, Takuya Yoshida, Kenjiro Higashi, Ayako Nakanome, Takenori Ogawa, Yukio Katori

Publication date 08-08-2021


Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m Twenty-seven patients achieved full-dose cisplatin (300 mg/m As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients.

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TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells

Liang Mao, Yao Xiao, Qi-Chao Yang, Shao-Chen Yang, Lei-Lei Yang, Zhi-Jun Sun

Publication date 02-08-2021


Anti-PD-1/PD-L1 therapy has recently been approved for head and neck squamous cell carcinoma (HNSCC). However, given that large numbers of patients with HNSCC do not respond to PD-1/PD-L1 antibodies, combination strategies for elevating the response rate need to be further investigated. The goal of this study was to explore the possibility of dual-targeting CD155/TIGIT and PD-1/PD-L1 signalling in HNSCC. Multiplex flow cytometry was performed to determine the co-expression of CD155 and PD-L1 in human HNSCC and transgenic HNSCC mouse models. The combined application of TIGIT m Ab and PD-L1 m Ab in a mouse model was used to explore the therapeutic effect. CD155 and PD-L1 were highly co-expressed on myeloid-derived suppressor cells (MDSCs) derived from patients with HNSCC and were inversely associated with the percentage of tumour CD3 Our study indicated that CD155

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Sensory recovery and oral health-related quality of life following tongue reconstruction using non-innervated radial forearm free flaps

Ling Zhu, Jinglu Zhang, Wenjing Chen, Peter Svensson, Kelun Wang

Publication date 06-08-2021


This study aimed to monitor the recovery of somatosensory function and oral health-related quality of life after tongue reconstruction using a non-innervated radial forearm free flap (RFFF). Twenty patients (9 men, age: 42-67 years) underwent tongue reconstruction with non-innervated RFFFs, and twenty age- and sex-matched controls were included in this study. Quantitative sensory testing (QST), including cold, warm, and mechanical detection thresholds (CDT, WDT, MDT); cold, heat, and mechanical pain thresholds (CPT, HPT, MPT); and static two-point, sharp/blunt, and direction discrimination (S2-PD, S/BD, DD) were determined 9 months and 18 months after surgery on the surgical (9 M, 18 M) and contralateral sides (9Mc, 18Mc). Oral Health Impact Profile-49 (OHIP-49) was used to determine the oral-related quality of life of participants. All parameters showed significantly lower sensitivity at 9 M and 18 M (p < 0.001) compared to those for the controls and the contralateral side, except for DD (p = 0.101). In addition, the parameters showed a significant decrease in sensitivity for 9Mc and 18Mc (p ≤ 0.043) compared to those for the controls, except for MPT, HPT, S/SD, and DD (p ≥ 0.453). Findings on WDT, MPT, S2-PD, and DD (p ≤ 0.046) indicated significantly higher somatosensory function at 18 M than that at 9 M. MDT and MPT (p ≤ 0.038) showed significantly higher sensitivity at 18Mc than at 9Mc. Scores for all dimensions of OHIP-49 were significantly higher in patients (decrease in quality of life, p ≤ 0.002) than in controls, except for physical discomfort (p = 0.51). However, the scores were significantly higher at 18 M than at 9 M (p ≤ 0.011), except for handicap (p = 0.36). Postoperative chemotherapy was significantly correlated with impaired thermal sensitivity of the flaps (WDT, p = 0.049). The present findings showed significant impairment in somatosensory function on both the surgical and contralateral sides of patients with RFFFs. However, a significant increase in somatosensory function was observed on both sides over time. Somatosensory disturbances observed after surgery were associated with poor oral health-related quality of life.

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Postoperative oral dysfunction following oral cancer resection and reconstruction: A preliminary cross-sectional study

Yuhei Matsuda, Tatsuo Okui, Masaaki Karino, Noriaki Aoi, Satoe Okuma, Kenji Hayashida, Tatsunori Sakamoto, Takahiro Kanno

Publication date 28-07-2021


Oral cancer treatment reportedly causes decreased oral function, but few studies have examined the effects of oral cancer treatment on oral function in depth. This study aimed to comprehensively evaluate the oral function after treatment and classify the conditions related to oral dysfunction in patients with oral cancer. We recruited participants, collected their background data, and evaluated their oral function from September 2019 to March 2021. Principal component analysis was used to identify the components of oral function measurement and oral health perception. Receiver operating characteristic analysis was performed to investigate the accuracy of oral function measurements in predicting oral intake and nutritional status. Fifty patients treated for oral cancer, including 33 (66.0%) males and 17 (34.0%) females, were included. Their median age was 71.0 years (interquartile range: 63.0-76.0). There were significant differences in oral dryness between males and females, occlusal force among different age groups, tongue pressure based on the tumor stage and performance of reconstructive procedures, and masticatory function and Eating Assessment Tool scores based on whether radiotherapy was performed (P < 0.05). The principal component analysis proposed that oral function measurements and subjective oral health perception could be divided into three main components (transport, oral hygiene, and occlusion type), which explain 61.5% of the variance of the phenomenon. A significant decrease in oral function after oral cancer treatment should be diagnosed as postoperative oral dysfunction. Postoperative oral dysfunction can be classified into three types, each of which may present with different pathologies.

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Robotic surgery may improve overall survival for T1 and T2 tumors of the hypopharynx: An NCDB cohort study

Andrey Finegersh, Rohith S. Voora, Bharat Panuganti, Farhoud Faraji, Floyd Christopher Holsinger, Kevin T. Brumund, Charles Coffey, Joseph Califano, Ryan K. Orosco

Publication date 31-07-2021


Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival. The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included. We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation. Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.

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A complete magnetic sentinel lymph node biopsy procedure in oral cancer patients: A pilot study

Eliane R. Nieuwenhuis, Barry Kolenaar, Alexander J.M. van Bemmel, Jurrit J. Hof, Joop van Baarlen, Anke Christenhusz, Joost J. Pouw, Bernard ten Haken, Lejla Alic, Remco de Bree

Publication date 31-07-2021


To assess the feasibility and merits of a complete magnetic approach for a sentinel lymph node biopsy (SLNB) procedure in oral cancer patients. This study included ten oral cancer patients (stage cT1-T2N0M0) scheduled for elective neck dissection (END). Superparamagnetic iron oxide nanoparticles (SPIO) were administered peritumorally prior to surgery. A preoperative MRI was acquired to identify lymph nodes (LNs) with iron uptake. A magnetic detector was used to identify magnetic hotspots prior, during, and after the SLNB procedure. The resected sentinel LNs (SLNs) were evaluated using step-serial sectioning, and the neck dissection specimen was assessed by routine histopathological examination. A postoperative MRI was acquired to observe any residual iron. Of ten primary tumors, eight were located in the tongue, one floor-of-mouth (FOM), and one tongue-FOM transition. SPIO injections were experienced as painful by nine patients, two of whom developed a tongue swelling. In eight patients, magnetic SLNs were successfully detected and excised during the magnetic SLNB procedure. During the END procedure, additional magnetic SLNs were identified in three patients. Histopathology confirmed iron deposits in sinuses of excised SLNs. Three SLNs were harboring metastases, of which one was identified only during the END procedure. The END specimens revealed no further metastases. A complete magnetic SLNB procedure was successfully performed in eight of ten patients (80% success rate), therefore the procedure seems feasible.
Recommendations for further investigation are made including: use of anesthetics, magnetic tracer volume, planning preoperative MRI, comparison to conventional technique and follow-up.

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Recurrence and malignant transformation rates of high grade oral epithelial dysplasia over a 10 year follow up period and the influence of surgical intervention, size of excision biopsy and marginal clearance in a UK regional maxillofacial surgery unit

Ciro Gilvetti, Chandni Soneji, Brian Bisase, Andrew William Barrett

Publication date 25-07-2021


To determine the overall recurrence rate (RR) and malignant transformation rate (MTR) of high grade oral mucosal epithelial dysplasias (HGOED). A clinicopathological review of records of patients diagnosed with a unifocal HGOED between 2004 and 2016 on incisional biopsy who then underwent excision. The mean duration of follow-up was 47.7 months (±29.9 SD). Full demographic, historical and histopathological data were available for 120 patients. Six were lost to follow-up after excisional biopsy. Invasive squamous cell carcinoma (SCC) was present in 19 (18.3%) excisions. HGOED affected the lateral and ventral tongue in 58% of patients. Fourteen (11.7%) were not treated surgically but kept under surveillance. The overall RR was 34.7% (33 patients) and MTR 17.8% (17 patients). Four of the 14 (28.6%) patients who had not had the HGOED excised developed SCC, by contrast to the 13 of the 106 (12.3%) who had been treated. RR was significantly associated with positive excision margins (p = 0.007; OR = 3.6) and a clinical presentation of erythroplakia (p = 0.023; OR = 1.5). MTR was significantly associated with age (p = 0.034), clinical appearance (p = 0.030), site (p = 0.007), treatment received (p = 0.012) and positive excision margins (p = 0.007). The mean time for recurrence to develop was 62 months (±31.5 SD) (range 22-144 months), that for malignant transformation was 50 months (±32.5 SD) (range 8-97 months). Patients with HGOED require follow-up for at least 10 years after treatment. Younger age, homogeneous clinical appearance, complete excision, a larger excision specimen and clear margins all improve prognosis.

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Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to carbon dioxide gas insufflation: A comparative analysis of 131 cases

Jun-Ook Park, Dong-hyun Lee, Mi Ra Kim, Sang-Yeon Kim, Jae Hong Han, Dong-Il Sun

Publication date 04-08-2021


Although transoral endoscopic thyroid surgery affords several advantages, the use of carbon dioxide (CO2) gas to create and maintain the working space may cause complications such as subcutaneous emphysema and a CO2 embolism. We have used a self-retaining retractor as an alternative to CO2 gas insufflation for some time; we here report its feasibility and safety. We reviewed the medical records of 131 patients who underwent transoral endoscopic thyroid lobectomy; we compared the "CO2 group" and the "retractor" group. All thyroid tumors were completely removed with negative surgical margins. No major complication occurred in the retractor group.
Two major events occurred in the CO2 group: one case of permanent vocal cord palsy and one CO2 embolism. Significant subcutaneous emphysema of the neck and chest were noted in 17.7% of CO2 group patients, but in no retractor group patient. Wound infection occurred in one patient in each group but improved after appropriate management. The total operation times from incision to suture did not differ significantly between the two groups (p = 0.514). Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to CO2 gas insufflation is feasible and safe. The superiority of transoral endoscopic thyroidectomy would be emphasized by avoiding CO2 gas insufflation, thus eliminating the risk of CO2 gas-related complications.

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The important role of cisplatin in the treatment of HPV-positive oropharyngeal cancer assessed by real-world data analysis

Irene H. Nauta, Thomas Klausch, Peter M. van de Ven, Frank J.P. Hoebers, Lisa Licitra, Tito Poli, Kathrin Scheckenbach, Ruud H. Brakenhoff, Johannes Berkhof, C. René Leemans

Publication date 27-07-2021


The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data. A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression. Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008). This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs.

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Surgeon practice patterns in transoral robotic surgery for HPV-related oropharyngeal cancer

Celeste Kim, Eduardo Martinez, Marta Kulich, Mark S. Swanson

Publication date 24-07-2021


Analyze how otolaryngologists approach HPV-related oropharyngeal cancer in terms of patient selection for transoral surgery, perceptions of treatment related risks and benefits, and adjuvant treatment decisions. A survey on HPV-related cancer management was distributed to otolaryngologists in the US through Red Cap. Differences in responses were analyzed using Pearson's chi-squared and Fisher's exact tests. A total of 111 out of 143 (77.6%) otolaryngologists completed the survey. Overall, most prefer treating T1/T2 tumors using transoral robotic surgery (TORS) and T3 tumors through primary radiation therapy (RT), though there were significant differences between cohorts. Non-fellowship-trained surgeons and those in community practices favored RT for T1/T2 more than their fellowship-trained and academic counterparts, respectively. For adjuvant treatment, non-fellowship-trained surgeons favored adjuvant CRT, whereas fellowship-trained surgeons preferred only adjuvant RT, for patients with lymphovascular or perineural invasion, >1 lymph node involvement, or close deep margins. TORS was viewed as having less adverse sequelae (i.e. dysphagia, dysphonia, xerostomia). Though the two modalities had similar oncologic outcomes, TORS was perceived as providing better quality of life (QOL). There are variations in HPV-related OPSCC management based on surgeon background and preferences across the US. TORS and primary RT are believed to offer similar oncologic control, but the former provides lesser adverse sequelae and better QOL. Additionally, surgeon demographics (i.e. fellowship status, practice type, and region) can affect management decisions, including patient selection for TORS and adjuvant therapy decisions. Further study is required to better understand and standardize appropriate HPV-positive OPSCC management.

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Biologic and behavioral associations of estrogen receptor alpha positivity in head and neck squamous cell carcinoma

Virginia Drake, Elaine Bigelow, Carole Fakhry, Melina Windon, Lisa M. Rooper, Patrick Ha, Brett Miles, Christine Gourin, Rajarsi Mandal, Wojciech Mydlarz, Nyall London, Peter S. Vosler, Siddhartha Yavvari, Tanya Troy, Tim Waterboer, David W. Eisele, Gypsyamber DSouza

Publication date 26-07-2021


Tumor HPV status is an established independent prognostic marker for oropharynx cancer (OPC). Recent studies have reported that tumor estrogen receptor alpha (ERα) positivity is also associated with prognosis independent of HPV. Little is known about the biologic and behavioral predictors of ERα positivity in head and neck squamous cell cancer (HNSCC). We therefore explored this in a multicenter prospective cohort study. Participants with HNSCC completed a survey and provided a blood sample. Tumor samples were tested for ERα using immunohistochemistry. ERα positivity was defined as ≥1%, standardized by the American Society of Clinical Oncology/College of American Pathologists in breast cancer. Characteristics were compared with χ Of 318 patients with HNSCC, one third had ERα positive tumors (36.2%, n = 115). Odds of ERα expression were significantly increased in those with HPV-positive tumors (OR = 27.5, 95% confidence interval[CI] 12.1-62), smaller tumors (≤T2, OR = 3.6, 95% CI 1.9-7.1), male sex (OR = 2.0, 95% CI 1.1-3.6), overweight/obesity (BMI ≥ 25, OR = 1.9, 95% CI 1.1-3.3), and those married/living with a partner (OR = 1.7, 95% CI 1.0-3.0). In a multivariate model, HPV-positivity (aOR = 27.5, 95% CI 11.4-66) and small tumor size (≤T2, aOR = 2.2, 95% CI 1.0-4.8) remained independently associated with ERα status. When restricted to OPC (n = 180), tumor HPV status (aOR = 17.1, 95% CI 2.1-137) and small tumor size (≤T2, aOR = 4.0 95% CI 1.4-11.3) remained independently associated with ERα expression. Tumor HPV status and small tumor size are independently associated with ERα expression in HNSCC.

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Percutaneous endoscopic gastrostomy can improve survival outcomes in patients with N3 nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy

Yun Xu, Mengwei Chen, Qiaojuan Guo, Hewei Peng, Lanyan Guo, Jingfeng Zong, He Huang, Bijuan Chen, Hanchuan Xu, Jianji Pan, Shaojun Lin

Publication date 17-07-2021


Our previous study revealed that percutaneous endoscopic gastrostomy (PEG) and intensive nutritional support may minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) during concurrent chemoradiotherapy (CCRT). This study aimed to further explore the potential long-term survival benefits of PEG in LA-NPC. Between June 1, 2010 and June 30, 2014, a total of 133 consecutive LA-NPC patients who received prophylactic PEG (pPEG) feeding before the initiation of CCRT were included. Meanwhile, an additional 133 non-PEG patients, who were matched for age; sex; and tumor, node, and metastases stage, were selected as control cohort. The log-rank test was used to compare survival distributions between groups. Multivariate prognosis analysis was conducted using a Cox's proportional hazards regression model. After a median follow-up time of 81 months (range: 4-119 months), pPEG was not associated with significant survival benefits in the whole cohort. However, the N3 NPC patients who underwent PEG had significantly higher 5-year overall survival (OS) and progression-free survival (PFS) (84.0 and 76.0%, respectively) than those who did not undergo PEG (56.7 and 45.6%, respectively; p < 0.05). Univariate and multivariate analyses demonstrated that PEG was an independent factor for N3 survival. PEG can maintain the nutritional status and improve the rate of treatment completion for LA-NPC patients who underwent CCRT, and these advantages can transfer into survival benefits in N3 NPC. Further multicenter prospective clinical trials are warranted.

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Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma

Yuancheng Li, Linnan Gong, Na Qin, Xiaoyu Wei, Limin Miao, Hua Yuan, Cheng Wang, Hongxia Ma

Publication date 16-07-2021


CircRNAs are critical gene modulators in tumor initiation and progression. However, the expression pattern and molecular pathogenesis of circRNAs in oral squamous cell carcinoma (OSCC) are still poorly characterized. RNA sequencing with CIRCexplorer2 pipeline was performed to identify circRNAs in 46 tumor-normal paired tissues from OSCC patients. Another set of 48 head and neck squamous cell carcinoma samples from the Mi Onco Circ database were utilized as an independent validation. Of the 1276 identified high-confidence circRNAs, 154 were differentially expressed between tumor and normal tissues (log CircRNAs showed a global down-regulation pattern in OSCC tissues, and genes regulated by circRNAs primarily involved in immune and extracellular matrix pathways, which could also affect the OSCC prognosis, indicating that they may serve as potential prognostic biomarkers.

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An overview of the current clinical status of optical imaging in head and neck cancer with a focus on Narrow Band imaging and fluorescence optical imaging

Jeroen E. van Schaik, Gyorgy B. Halmos, Max J.H. Witjes, Boudewijn E.C. Plaat

Publication date 29-08-2021


Early and accurate identification of head and neck squamous cell carcinoma (HNSCC) is important to improve treatment outcomes and prognosis. New optical imaging techniques may assist in both the diagnostic process as well as in the operative setting by real-time visualization and delineation of tumor. Narrow Band Imaging (NBI) is an endoscopic technique that uses blue and green light to enhance mucosal and submucosal blood vessels, leading to better detection of (pre)malignant lesions showing aberrant blood vessel patterns. Fluorescence optical imaging makes use of near-infrared fluorescent agents to visualize and delineate HNSCC, resulting in fewer positive surgical margins. Targeted fluorescent agents, such as fluorophores conjugated to antibodies, show the most promising results.
The aim of this review is: (1) to provide the clinical head and neck surgeon an overview of the current clinical status of various optical imaging techniques in head and neck cancer; (2) to provide an in-depth review of NBI and fluorescence optical imaging, as these techniques have the highest potential for clinical implementation; and (3) to describe future improvements and developments within the field of these two techniques.

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Canadian consensus statement on the management of radioactive iodine–resistant differentiated thyroid cancer

Andrée Boucher, Shereen Ezzat, Sebastien Hotte, Irina Rachinsky, Murali Rajaraman, Dean Ruether, Sam M. Wiseman, James Brierley, Cheryl Ho, Monika Krzyzanowska, Nathan Lamond, Marie-Hélène Massicotte, Shereen Joseph, Kassey Herscovitch, Lindsey Sikora, Eric Winquist

Publication date 14-08-2021


Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

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Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics

Ambika Chamoli, Abhishek S. Gosavi, Urjita P. Shirwadkar, Khushal V. Wangdale, Santosh Kumar Behera, Nawneet Kumar Kurrey, Kiran Kalia, Amit Mandoli

Publication date 31-07-2021


Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy of the oral cavity. The substantial risk factors for OCSCC are the consumption of tobacco products, alcohol, betel quid, areca nut, and genetic alteration. However, technological advancements have occurred in treatment, but the survival decreases with late diagnosis; therefore, new methods are continuously being investigated for treatment. In addition, the rate of secondary tumor formation is 3-7% yearly, which is incomparable to other malignancies and can lead to the disease reoccurrence. Oral cavity cancer (OCC) arises from genetic alterations, and a complete understanding of the molecular mechanism involved in OCC is essential to develop targeted treatments. This review aims to update the researcher on oral cavity cancer, risk factors, genetic alterations, molecular mechanism, classification, diagnostic approaches, and treatment.

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Management and outcome of middle ear adenomatous neuroendocrine tumours: A systematic review

M.S.D. Engel, R.J.L. van der Lans, J.C. Jansen, C.R. Leemans, E. Bloemena, B.I. Lissenberg-Witte, J.A. Rijken, C.F. Smit, E.F. Hensen

Publication date 06-08-2021


Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using Pub Med, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted.

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Adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Finding the suitable population

Bi-Cheng Wang

Publication date 02-10-2021


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Dentinogenic ghost cell tumor with focal atypical features suggesting ghost cell odontogenic carcinoma: Report of a challenging diagnosis

Danielle Castex Conde, Gustavo de Souza Vieira, Pâmella de Pinho Montovani, João Pedro Roque Beserra, Mauro César Gaspar Ribeiro, Rafaela Elvira Rozza-de-Menezes, Karin Soares Cunha

Publication date 18-09-2021


Dentinogenic ghost cell tumor (DGCT) represents a rare benign odontogenic neoplasm that can appear in a central or peripheral form and may rarely undergo malignant transformation to ghost cell odontogenic carcinoma (GCOC). We aim to report a case of a central DGCT with focal cytological malignant aspects. A 24-year-old woman exhibited a painful enlargement and dental mobility in the left posterior maxilla for about one year, which appeared as an expansive well-defined hypodense maxillary image with hyperdense foci invading ipsilateral maxillary sinus. Incisional biopsy showed a predominantly solid hyperchromatic basaloid epithelium presenting cellular pleomorphism and mitotic activity, admixed with abundant ghost cell aggregates and dentinoid material. The lesion was immunopositive for p53 and had 21% of Ki-67 proliferation index (PI). These microscopic features suggested initially a GCOC diagnosis. Partial left maxillectomy was performed without complications. The surgical specimen presented an exuberant variation of the epithelial parenchyma, including ameloblastomatous, fusiform, and cribriform areas, with numerous ghost cells and dentinoid material, lacking any signs of malignancy. The final diagnosis was DGCT. The patient is in a strict regular follow-up for over two years, and there are no signs of recurrence.

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