External Auditory Canal Squamous Cell Research Articles

Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

Treatment outcome and prognostic factors of external auditory canal squamous cell carcinoma: A retrospective study in a tertiary center.

Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare malignancy with various treatment strategies and outcomes. The purpose of this study was to evaluate the clinical characteristics and survival outcomes and identify prognostic factors in patients with SCC of EAC. Twenty-one patients with SCC of EAC treated in a single tertiary center between 2009 and 2021 were retrospectively reviewed and analyzed. The modified Pittsburgh classification system was applied for staging. Factors associated with survival were identified by univariate survival analysis. The mean age at diagnosis was 61 years (range: 41-79 years). Early-stage (T1 + T2) accounts for 38.1% of the series and advanced-stage (T3 + T4) accounts for 61.9%. Eighteen (85.7%) patients underwent primary surgery with curative intent. The 5-year overall survival rate of the 21 patients was 67.4%. Tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura were associated with poor prognosis in univariate analysis (p = .046; .008; .027; and .08, respectively). Factors predictive of less favorable survival include the history of COM, tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura. It is important to make a precise and systemic preoperative evaluation of disease extent. 4.

Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma.

Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

Clinical outcomes of temporal bone squamous cell carcinoma: A single-institution experience.

This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan-Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)- T classifications had a poorer prognosis (T3 vs. T1-2: HR: 2.81, 95% CI: 0.34-23.43; T4 vs. T1-2: HR: 7.25, 95% CI: 0.95-55.41; p=0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04-6.76, p=0.04). MESCC and advanced MPB-T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC.

The Efficacy of Radiotherapy without Surgery for External Auditory Canal Squamous Cell Carcinoma.

External auditory canal (EAC) cancer is a rare disease for which there are no adequate evidence-based treatment strategies. Radiotherapy is often used as the initial treatment to preserve the organ. This study aimed to elucidate the efficacy of radiotherapy for EAC squamous cell carcinoma (SCC). Patients with T1 disease were treated with radiotherapy alone. Patients with T2–4 disease were treated with chemoradiotherapy. The median follow-up period was 30.4 months. The 3-year local control (LC) rate for all patients was 51%, the disease-free survival (DFS) rate was 44%, and the overall survival (OS) rate was 73%. For T1–3 disease, the 3-year LC rate was 74%, DFS was 62%, and OS was 89%. However, for T4 disease, the 3-year LC rate was 17%, DFS was 17%, and OS was 50%. In a univariate analysis, only the T-category was a significant factor for LC and DFS (p = 0.006 and 0.02, respectively). All local recurrences were within the high-dose irradiated area. The results of this study suggest chemoradiotherapy can be an alternative to a combination of surgery and postoperative radiation for T1–3 SCC of the EAC. However, the efficacy of chemoradiotherapy in T4 cases was inadequate.

Association of gene mutations with clinicopathologic features in patients with external auditory canal squamous cell carcinoma.

External auditory canal squamous cell carcinoma (EACSCC) is a rare form of malignant tumor. Due to the extremely limited understanding of the genomic landscape in EACSCC, the association between gene mutations and clinicopathologic features remains unclear. This study aimed to explore somatic gene mutations associated with the clinicopathological features in patients with EACSCC, and to identify the candidate gene mutations for predicting survival outcome in EACSCC. Twenty-two tissue samples obtained from patients with EACSCC were analyzed for genetic mutations based on targeted next-generation sequencing and genetic expression based on IHC staining to investigate the driver of tumorigenesis and/or the candidates of genes for predicting clinical outcome in EACSCC. Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). TP53 mutations showed significant correlation with T classification (P = 0.027) and p53 expression phenotype (P < 0.001). The 5-year overall survival (OS) rates for EACSCC patients with TP53 mutations and wild-type TP53 were 45.0% and 75.0%, respectively. Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of OS rates for EACSCC patients (P = 0.007). This study has suggested that TP53 mutations have potential for use as a biomarker for identifying individuals at high risk of developing tumors and for predicting survival outcome in EACSCC. IHC staining for p53 might play a useful role as screening tool for detecting TP53 mutations in patients with EACSCC.

MiR-34a predicts the prognosis of advanced-stage external auditory canal squamous cell carcinoma

Background External auditory canal (EAC) squamous cell carcinoma (SCC) is a rare disease, and the survival rate is low in the advanced stages. It has been reported that miR-34a expression is low in many cancers and acts as a tumor suppressor, but its function in EACSCC has not yet been reported. Aims To analyze the miR-34a expression levels in EACSCC specimens using in situ hybridization (ISH). Material and Methods We performed microRNA ISH for miR-34a detection and immunohistochemical analysis of p53 and Ki67 in the EACSCC and otitis externa (OE) specimens. Results miR-34a was expressed in the basal and suprabasal layers in the OE epidermis. The pronounced expression of miR-34a was observed in the two cases of T2 (Stage II). In the one case of T3 (Stage III), it was almost the same as that of the OE. On the other hand, the expression levels of miR-34a in the one case of T3 (Stage IV) and two cases of T4 (Stage IV) were apparently reduced. Conclusion We demonstrated that the expression level of miR-34a was higher in early-stage EACSCC and lower in advanced-stage EACSCC. Significance The expression level of miR-34a may predict a prognosis in patients with advanced-stage EACSCC.

A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition.

To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents. Preclinical translational research. Biomedical research institute. The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed. CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM. This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.

Targeted molecular characterization of external auditory canal squamous cell carcinomas.

HypothesisSquamous cell carcinomas (SCC) of the external auditory canal (EAC) may harbor unique genomic alterations that may explain aggressive behavior and differentiate these tumors from cutaneous SCCs of other subsites.BackgroundEAC SCCs arise in a non‐ultraviolet‐exposed region of the head and neck, are often locally aggressive and may metastasize to lymph nodes or distant sites. The genomic alterations underlying cutaneous SCC of other sites are well‐documented; however, mutational profiles of EAC SCC are less well characterized and may contribute to the unique anatomic site, high rates of recurrence and tumor spread. We performed targeted sequencing of a cohort of primary EAC SCCs to identify recurring and potentially targetable genomic alterations.MethodsGenomic DNA was extracted from formalin‐fixed paraffin‐embedded specimens of 7 EAC SCCs and subjected to targeted DNA sequencing using a 227‐gene panel. Somatic alterations and gene copy number alterations were annotated using our validated, in‐house bioinformatics pipelines.ResultsIn our EAC SCCs, we found recurrent alterations in TP53 and genes of receptor tyrosine kinase (eg, EGFR, FGFR) and PI3K pathways (eg, PIK3CA), similar to cutaneous SCCs of other head and neck sites. We also observed a high frequency of telomerase reverse transcriptase amplification and DNA methyltransferase 1 alterations, both of which are rarely observed in cutaneous SCCs of other sites.ConclusionThese data represent the first step toward precise molecular characterization of EAC SCCs that may lead to an enhanced understanding of tumor biology and modernized precision medicine approaches for unique tumors.Level of Evidence: NA

Establishment and characterization of a primary cell culture derived from external auditory canal squamous cell carcinoma.

There are no human cancer cell lines of external auditory canal origin available for research use. This report describes the establishment of a culture condition for external auditory canal squamous cell carcinoma, derived from human tumor tissue. Successive squamous cell carcinoma colonies were dissociated by trypsin, subcultured, and maintained on a feeder layer (MMC‐TIG‐1‐20), yielding a clonally proliferating cell culture. Two morphological types of colony were observed: (a) densely packed colonies and (b) colonies with indistinct boundaries characterized by cell–cell complexes with fibroblast feeder cells. The SCC‐like characteristics of these cells were evidenced by positivity for p53, SCCA1/2, cytokeratin, and vimentin, and cancer stem cell properties were indicated by positivity for CD44, CD133, Oct3/4, and alkaline phosphatase (ALP). One of the unique properties of cell cultures is their tendency to form steric colonies in vitro on feeder layer cells. In addition, in the presence of fresh macrophages, the cells very slowly transform to break away from colonies as free cells, a process that resembles the epidermal–mesenchymal transition, whereby cell–cell interactions are weakened and migration activity is enhanced. These factors are purported to play a key role in cancer cell metastasis.

Short-term Outcomes of 40 Cases of External Auditory Canal Squamous Cell Carcinomas Treated at a Single Institution

Short-term Outcomes of 40 Cases of External Auditory Canal Squamous Cell Carcinomas Treated at a Single Institution

A systematic review of the primary squamous cell carcinoma of the external auditory canal: survival outcome based on T-staging and proposal of a new classification.

This study aimed to provide a systematic review on survival outcome based on Pittsburgh T-staging for patients with primary external auditory canal squamous cell carcinoma. This study was a systematic review in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed until January 2018; pertinent studies were screened. Quality of evidence was assessed using the grading of recommendation, assessment, development and evaluation working group system. Eight articles were chosen that reported on 437 patients with external auditory carcinoma. The 5-year overall survival rate was 53.0 per cent. The pooled proportion of survivors at 5 years for T1 tumours was 88.4 per cent and for T2 tumours was 88.6 per cent. For the combined population of T1 and T2 cancer patients, it was 84.5 per cent. For T3 and T4 tumours, it was 53.3 per cent and 26.8 per cent, respectively, whereas for T3 and T4 tumours combined, it was 40.4 per cent. Individual analysis of 61 patients with presence of cervical nodes showed a poor survival rate. From this review, there was not any significant difference found in the survival outcome between T1 and T2 tumours. A practical classification incorporating nodal status that accurately stratifies patients was proposed.

Genetic landscape of external auditory canal squamous cell carcinoma.

External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA‐editing enzyme catalytic polypeptide‐like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm‐level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.

Prognostic value of pre-operative peripheral inflammation markers in patients with squamous cell carcinoma of the external auditory canal

IntroductionSquamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. ObjectiveThis study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. MethodsWe retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. ResultsA total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p < 0.0001, p < 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. ConclusionsPre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease.

Radical brachytherapy for early-stage external auditory canal squamous cell carcinoma: A dosimetric feasibility study using plastic earbud as an applicator

Squamous cell carcinoma (SCC) of external auditory canal (EAC) is extremely rare. Although surgery followed by radio (chemo) therapy is the contemporary standard of care, radical radio (chemo) therapy has been successfully used as an anatomical as well as functional organ preservation modality. Radical brachytherapy is a promising alternative in early-stage SCC-EAC. We report our initial experience on the feasibility of using commercially available plastic earbud along with soft flexible earpiece of stethoscope as a radioactive source career applicator of remote after-loading high-dose rate radioactive sources (Ir192).

Treatment outcomes of local advanced external auditory canal squamous cell carcinomas

Treatment outcomes of local advanced external auditory canal squamous cell carcinomas

Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.

Expression profiling of long noncoding RNA identifies lnc-MMP3-1 as a prognostic biomarker in external auditory canal squamous cell carcinoma.

Our previous studies suggested external auditory canal squamous cell carcinoma (EACSCC) is a rare malignancy with heterogeneous outcomes. This study aimed to identify lncRNA profile of EACSCC and determine the clinical application. Differential expression genes (DEGs) were investigated in EACSCC by whole transcriptome lncRNA arrays (GPL23178). RT‐PCR was used to quantify the microarray data. Bioinformatics analyses were performed to evaluate DEGs regulations in gene ontology and cellular pathways. Fluorescence in situ hybridization (FISH) was utilized to validate lncRNA expression. The overall survival was determined by Kaplan–Meier and log‐rank analyses. Our microarrays data had been submitted to Gene Expression Omnibus (GSE98912). We identified 5621 DEGs (3185 mRNAs, 2436 lncRNAs) in EACSCC. Lnc‐MMP3‐1 was the top one upregulated lncRNA in EACSCC with fold change of 237.2 (P < 0.001). RT‐PCR results showed similar expression levels as microarrays data. Bioinformatics analyses indicated development of EACSCC was involved in aberrant alternations of multiple biological processes and cellular pathways. FSIH assays also found lnc‐MMP3‐1 was significantly differentially overexpressed in EACSCC (P < 0.001). Tumor lnc‐MMP3‐1 levels were closely associated with differentiation degree (P = 0.016), tumor invasion (P = 0.015) and TNM stage (P = 0.015). Moreover, lnc‐MMP3‐1 expression was a significant prognostic factor in EACSCC (χ 2 = 4.276, P = 0.039). The study is the first screening and analysis of lncRNAs profile in EACSCC and provides new insights into pathogenesis of this rare disease. Our findings offered convincing evidences that lnc‐MMP3‐1 is a novel survival predictor of EACSCC patients.

Right dominance in the incidence of external auditory canal squamous cell carcinoma in the Japanese population: Does handedness affect carcinogenesis?

Objectives/HypothesisTo investigate the relationship between handedness and the incidence of squamous cell carcinoma in the external auditory canal (EACSCC).Materials and MethodsSixty‐eight cases of EACSCC were enrolled in this study, and their affected side was checked. Handedness and ear‐picking habits were also investigated in 34 EACSCC cases. Handedness was judged based on self‐categorization, and the relationship between handedness and the affected side was investigated.ResultsFifty‐two cases occurred on the right side, and 16 cases occurred on the left side of patients with EACSCC. The incidence of laterality in EACSCC showed a statistically significant right dominance. Concerning handedness, 29 cases were right‐handed, 4 cases were left‐handed, and 1 case was ambidextrous. Twenty‐seven out of the 29 right‐handed cases and 1 ambidextrous case suffered from carcinoma on the right side, whereas 3 left‐handed cases suffered from carcinoma on the left side. That is, most of the cases suffered from EACSCC on the same side as their handedness, and this tendency showed a statistically significant difference. Most of the patients with EACSCC experienced itching and habitual ear‐picking in the affected side.ConclusionMechanical stimulations to the EAC, such as ear picking, may plausibly cause EACSCC. In Japan, ear picking, also called “mimikaki,” is a popular habit and an established unique culture. Because ear picking requires delicate handling and manipulation, this tends to occur on the same side as the handedness in the Japanese population. This is the first report about the relationship between handedness and carcinogenesis.Level of EvidenceN/A.

Clinical Characteristics and Management of External Auditory Canal Squamous Cell Carcinoma in Post-Irradiated Nasopharyngeal Carcinoma Patients.

To describe the clinical characteristics and management of patients with external auditory canal (EAC) squamous cell carcinoma (SCC) that arose after they received radiotherapy for nasopharyngeal carcinoma (NPC) and to compare them with primary EAC SCC patients. Retrospective clinical analysis. Hospital. Nine irradiated NPC patients who subsequently developed secondary EAC SCC and 41 primary EAC SCC patients at a single hospital. Clinical characteristics and management outcomes of patients were reviewed. Clinical manifestations, regions of tumor involvement, the pathological staging, cumulative overall survival rates, Kaplan-Meier method, log rank test, and Mann-Whitney U test. The most common symptoms of both groups were otorrhea, otalgia, and hearing loss. The region most involved in both groups was the EAC. The proportions of early stage (T1,T2) tumors in the post-irradiated and primary EAC SCC group were 56 and 22%, respectively. The 6-month, 1-year, 2-year, and 3-year cumulative overall survival rates of the post-irradiated EAC SCC group were 100, 100, 89, and 89%, respectively. The incidence of radionecrosis was higher in the post-irradiation EAC SCC group than in the primary EAC SCC group. Post-irradiation EAC SCC has similar symptoms and invades similar regions as primary EAC SCC. The proportion of early stage tumors in the post-irradiated EAC SCC group was higher than that in the primary EAC SCC group. High incidence of radionecrosis was observed after the second course of radiotherapy. Aggressive surgical treatment is strongly recommended, but adjuvant radiotherapy for early stage EAC SCC should be provided cautiously.