High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

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Current Role of Radiotherapy in the Management of Oral Cavity Squamous Cell Carcinoma

Craniomaxillofacial Trauma & Reconstruction ◽

10.1177/1943387520971418 ◽

2020 ◽

pp. 194338752097141

Author(s):

William M. Mendenhall ◽

Adam L. Holtzman ◽

Roi Dagan ◽

Curtis M. Bryant ◽

Kathryn E. Hitchcock ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Advanced Disease ◽

Current Role ◽

Extranodal Extension ◽

Postoperative Setting ◽

Extent Of Disease

Study Design: Literature review. Objective: To review the current role of radiotherapy (RT) in the management of oral cavity squamous cell carcinoma (SCC). Methods: Review of selected literature. Results: T1-T2N0 SCCs may be treated with either RT alone or surgery with a high likelihood of cure. The pendulum swung toward surgery with postoperative RT (PORT) added depending on the pathological findings in the mid 1980s. Patients with positive margins, extranodal extension (ENE), and/or 4 or more positive nodes receive concomitant chemotherapy (POCRT). Patients with T3-T4 and/or positive regional nodes are treated with surgery and PORT alone or POCRT. The likelihood of cure is moderate to low depending on extent of disease. The likelihood of major complications ranges from 10% to 30% depending on the method of reconstruction and the aggressiveness of postoperative PORT/POCRT. Patients with very advanced disease are treated with palliative RT, chemotherapy, or supportive care. Conclusions: The role of RT in the management of oral cavity SCC is primarily in the postoperative setting with palliative RT being reserved for those with very advanced disease where the likelihood of cure is remote.

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The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity

Radiation Oncology ◽

10.1186/1748-717x-7-215 ◽

2012 ◽

Vol 7 (1) ◽

pp. 215 ◽

Cited By ~ 65

Author(s):

Din-Li Tsan ◽

Chien-Yu Lin ◽

Chung-Jan Kang ◽

Shiang-Fu Huang ◽

Kang-Hsing Fan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Weekly Cisplatin

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Postoperative radiotherapy for patients at high risk of recurrence of oral cavity squamous cell carcinoma

The Laryngoscope ◽

10.1002/lary.24938 ◽

2014 ◽

Vol 125 (3) ◽

pp. 630-635 ◽

Cited By ~ 12

Author(s):

Michael P. Herman ◽

Roi Dagan ◽

Robert J. Amdur ◽

Christopher G. Morris ◽

John W. Werning ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Postoperative Radiotherapy ◽

Risk Of Recurrence

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Characteristics of the course of squamous cell carcinoma of the oral cavity depending on the HPV status.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17579 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17579-e17579

Author(s):

Pavel V. Svetitskiy ◽

Tatiana A. Zykova ◽

Viktoriya L. Volkova ◽

Irina V. Aedinova

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Hpv Infection ◽

Lower Grade ◽

Tumor Tissues ◽

Hpv Status ◽

Formalin Fixed Paraffin Embedded

e17579 Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.

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A study of chemoradiotherapy with high dose cisplatin for postoperative high-risk squamous cell carcinoma of oral cavity

Annals of Oncology ◽

10.1093/annonc/mdv472.134 ◽

2015 ◽

Vol 26 ◽

pp. vii135

Author(s):

Toshihiro Arai ◽

Yoshihide Ota ◽

Takayuki Aoki ◽

Mitsunobu Otsuru

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

High Dose

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Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

Oral Oncology ◽

10.1016/j.oraloncology.2014.11.011 ◽

2015 ◽

Vol 51 (3) ◽

pp. 229-236 ◽

Cited By ~ 45

Author(s):

H. Mirghani ◽

F. Amen ◽

F. Moreau ◽

J. Lacau St Guily

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Human Papillomaviruses

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Regional metastasis to anatomies beyond traditional neck dissection boundaries: a multi-institutional analysis focused on unconventional metastases in oral cancer patients

World Journal of Surgical Oncology ◽

10.1186/s12957-020-02057-6 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Weijin Gao ◽

Zhuowei Tian ◽

Xiaodan Fang ◽

Jincai Xue ◽

Zhixiang Li ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Lymph Nodes ◽

Cell Carcinoma ◽

Squamous Cell ◽

Metastatic Lymph Nodes ◽

Extranodal Extension ◽

Regional Metastasis ◽

Metastatic Lymph

Abstract Background Regional metastasis sometimes occurs in anatomies that are not included in traditional neck dissections. The purpose of this study was to evaluate the treatment outcomes of squamous cell carcinoma of oral cavity (SCCOC) patients with unconventional metastatic lymph nodes (UMLNs) in sublingual, buccinator, and parotid anatomies. Methods This retrospective multi-institutional analysis of squamous cell carcinoma of oral cavity patients with unconventional metastatic lymph nodes was performed from January 2008 to December 2015. All the included patients received surgical treatment for unconventional metastatic lymph nodes. The end point of the study was to determine the factors influencing these patients’ survival and the corresponding solutions to improve survival. Pathological grade, contralateral metastasis, extranodal extension, and other factors were collected and analyzed by logistic regression and the Cox model. Results A total of 89 patients were identified. Among these patients, 25 (28.1%) received primary treatment, 28 (31.5%) received staged (therapeutic) neck dissections, and 36 (40.4%) had recurrent or residual diseases. Altogether, 45 patients (51%) had buccinator node metastases, 31 (35%) had sublingual metastases, 12 (14%) had parotid metastases, and 1 had both buccinator and parotid metastases. Regarding regional metastases, 31 patients (34.8%) had isolated unconventional metastatic lymph nodes. Adjuvant therapies were administered to 72 (80.9%) patients, 25 (28.1%) of whom were treated with radio-chemotherapies. The overall survival rate was 38.2%. Multivariate analysis found that the subsites of unconventional metastatic lymph nodes (P = 0.029), extranodal extension in both unconventional metastatic lymph nodes (P = 0.025) and cervical lymph nodes (P = 0.015), sites of primary or recurrent squamous cell carcinoma of oral cavity (P = 0.035), and types of neck dissections (P = 0.025) were significantly associated with overall survival. Conclusions Unconventional metastatic lymph nodes are uncommon, yet awareness of potential unconventional metastatic lymph nodes should be heightened. Early surgical interventions are warranted in patients with sublingual or buccinator metastases, while caution should be given to those with parotid metastases. Aggressive en bloc (in-continuity) resections may be mandatory in advanced oral cancer cases for close anatomic locations with possible buccal or sublingual metastases.

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Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_320939 ◽

2021 ◽

pp. 265-278

Author(s):

Shao Hui Huang ◽

Rebecca Chernock ◽

Brian O’Sullivan ◽

Carole Fakhry

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Risk Stratification ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Distant Metastasis ◽

Neck Squamous Cell Carcinoma ◽

Extranodal Extension ◽

Pathology Specimen

Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

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