Evaluation of excisional biopsy for stage I and IIsquamous cell carcinoma of the oral cavity

Background. To reduce the risk of spreading tumor cells by incisional biopsy, we have employed excisional biopsy for early oral squamous cell carcinomas (SCCs). However, whether excisional biopsy should be adopted as a radical treatment for oral carcinomas is still controversial. Methods. Fifty-eight patients with stage I or II SCC of the oral cavity treated by excisional biopsy were reviewed clinicopathologically to investigate treatment outcome. Results. Eight of the 58 patients had a recurrence at the primary site and 7 had a secondary lymph node metastasis in the neck; all patients were curable by salvage treatment. We found a significant correlation between local recurrence and margin status and between tumor size and depth invasion. The absence or presence of epithelial dysplasia adjacent to the cancer was also important in predicting local recurrence. Endophytic tumors had a higher rate of neck metastasis than superficial or exophytic tumors (P < 0.001). Conclusions. Excisional biopsy is an effective and less invasive treatment for small oral SCCs. For superficial tumors that are frequently accompanied by epithelial dysplasia, tumors less than 30mm in size should be excised at a margin of 5 mm or more from the lesion, thereby including the dysplasia. Considering the positive correlation between tumor size and depth of invasion, exophytic tumors less than 20 mm in size can be treated by excisional biopsy alone. As endophytic tumors are highly aggressive and have a high propensity to metastasize to cervical lymph nodes, endophytic tumors less than 15 mm in size are indicated for excisional biopsy.     

早期口腔鳞癌颈部淋巴结转移的研究进展

口腔鳞癌具有较高的隐匿性颈淋巴结转移率,然而,临床上对早期患者颈部淋巴结的处理还存在较大争议.从肿瘤原发灶浸润厚度、影像学方面探讨早期口腔鳞癌颈部淋巴结转移的因素.对肿瘤原发灶浸润厚度>4 mm的患者,结合肿瘤影像学检查,建议行选择性颈部淋巴结清扫术.     

Immunohistochemical study on overexpression of cyclooxygenase-2 in squamous cell carcinoma of the oral cavity: its importance as a prognostic predictor

Cyclooxygenase-2 (COX-2) is known as one of the critical prognostic factors in carcinomas of the various organs. However, the importance of COX-2 overexpression in oral squamous cell carcinomas has not been fully described yet. We investigated overexpression of COX-2 by immunohistochemistry in 72 surgical specimens from patients with squamous cell carcinoma of the oral cavity, and evaluated correlations between COX-2 overexpression and clinicopathologic variables. The immunoreactivity of COX-2 was cytoplasmic. COX-2 overexpression was observed in 10 (13.9%) of 72 tumours and it was well correlated with lymph node involvement at the time of surgical treatment (P=0.011) and postoperative recurrence (P=0.025), but not with the other clinicopathologic variables including age, gender, tumour stage and histological grade. In addition, COX-2 overexpression showed a close association with postoperatively disease-free survival (P=0.039) and overall survival as well (P=0.043), and multivariate analyses revealed that COX-2 overexpression was an independent predictor for disease-free survival but not for overall survival. The current study suggests that overexpression of COX-2 could impact on disease-free survival for patients with oral squamous cell carcinoma and that selective inhibition of COX-2 is a possible target for the therapeutic strategies.     

Outcome analysis of patients with well-differentiated oral cavity squamous cell carcinoma

The prognosis of well-differentiated oral cavity squamous cell carcinoma (OSCC) is better than less-well-differentiated neoplasms. The aim of this retrospective study was to identify prognostic factors in patients with well-differentiated OSCC. The 5-year outcomes of 467 patients with well-differentiated OSCC who underwent radical surgery and neck dissection were analyzed. In the entire cohort, the presence of pathological node metastases (pN+ vs. pN0) was an independent predictor of 5-year outcomes. In pN0 patients, tumor depth (?8 mm) was the only independently prognostic factor for 5-year survival rates on multivariable analysis (disease-free survival [DFS], P = 0.001, hazard ratio [HR] = 2.634, 95% confidence interval [95% CI] = 1.496–4.636; disease-specific survival [DSS], P < 0.001, HR = 6.794, 95% CI = 2.364–19.525). In pN+ patients, level IV/V neck nodal metastases (DFS, P < 0.001, HR = 47.483, 95% CI = 8.942–252.122; DSS, P < 0.001, HR = 14.301, 95% CI = 5.337–38.323), and ?3 positive nodes (DFS, P = 0.037, HR = 2.107, 95% CI = 1.047–4.242; DSS, P = 0.044, HR = 2.093, 95% CI = 1.020–4.295) were independently associated with 5-year outcomes. Our results suggest that a tailored treatment approach in well-differentiated OSCC patients should take into account the presence of either pN0 or pN+ disease.     

Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavity

BACKGROUND: The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors. METHODS: For this report, the authors retrospectively reviewed data from 889 consecutive patients with OSCC who underwent radical surgery from January 1996 to November 2004. Patients were divided into 2 groups according to whether they had either achieved locoregional control (Group A; n = 678 patients) or developed a locoregional recurrence (Group B; n = 211 patients). Cox proportional-hazards models were used to identify independent predictors of the 5-year DM rate. RESULTS: In the entire study cohort, the 5-year DM rate was 9.6% (6.6% for Group A and 21.4% for Group B). In Group A, the number of positive lymph nodes (> or =5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage > or =III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators. CONCLUSIONS: The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery.     

口腔舌鳞状细胞癌的临床分析

目的:总结口腔舌鳞状细胞癌的治疗经验以指导临床。方法:回顾性分析1975年1月～2000年12月初次在我院诊治的329例口腔舌鳞状细胞癌患者的临床资料。T1病变82例,T2病变190例,T3病变43例,T4病变14例。综合治疗186例,单纯手术84例,单纯放疗59例。结果:91例患者组织学检查颈部淋巴结转移,其中Ⅰ区淋巴结转移36例,Ⅱ区淋巴结转移65例,Ⅲ区淋巴结转移18例,Ⅳ区淋巴结转移10例。T1病变患者5年和10年累积生存率分别为72.23%和65.21%,T2分别为38.38%和33.11%,T3分别为10.63%和10.63%,T4分别为7.14%和7.14%(P=0.0000,Logrank=75.99)。单纯手术组患者5年和10年累积生存率分别为56.13%和47.28%,单纯放疗组分别为17.49%和17.49%,综合治疗组分别为43.51%和39.04%(P=0.0000,Logrank=42.23)。结论:口腔舌鳞状细胞癌早期病变可考虑单纯手术,而中晚期应给予综合治疗,对中晚期cN0患者可考虑扩大的肩胛舌骨肌上清扫术。     

Oral cavity squamous cell carcinoma in 260 patients aged 80 years or more

Purpose

We report the experience of two French cancer centers in the treatment of oral cavity squamous cell carcinoma (SCC) in patients aged ?80 years.

Materials and methods

Two hundred and sixty patients aged ?80 years with a primary oral cavity SCC were included in this retrospective analysis.

Results

Sex ratio was near to 1. Tobacco or alcohol intoxication was the main risk factor for 66% of men and 16% of women and leukoplakia, lichen planus, or oral traumatism for 55% of women and 11% of men (p < 0.0001). Two hundred patients received a loco-regional (LR) treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent and 31 did not receive a LR treatment. Curative treatments were initially planned to be adapted to age in 118 patients (59%). The median disease-specific survival (DSS) was 29 months. In multivariate analysis, the independent prognostic factors for DSS were stage (HR = 0.42 [0.24-0.72]), age (HR = 0.43 [0.24-0.75]) and performance status (HR = 0.50 [0.27-0.95]). The median overall survival (OS) was 14 months. In multivariate analysis, the independent prognostic factors for OS were age (HR = 0.52 [0.35-0.79]), stage (HR = 0.56 [0.38-0.84]), tumor differentiation (HR = 0.60 [0.33-0.93]) and performance status (HR = 0.6 [0.37-0.97]). In patients treated with a curative intent, treatment adapted to age was not associated with a decreased overall survival or disease-specific survival as compared with the standard treatment. However, prophylactic lymph node treatment in stages I-II tumors decreased the rate of nodal recurrence from 38% to 6% (p = 0.01).

Conclusion

This study emphasizes the need for prospective evaluation of standard and adapted schedules in elderly patients with oral cavity cancer.     

Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma

Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p < 0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p < 0.001), positive N status (p < 0.001), advanced TNM stage (p < 0.001) and male gender (p = 0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p < 0.001), advanced T stage (p < 0.001), positive N status (p < 0.001) and advanced TNM stage (p < 0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p < 0.001) and osteopontin immunostaining was marginally significant for survival (p = 0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.     

Neoadjuvant treatment for esophageal squamous cell carcinoma

Squamous cell carcinoma and adenocarcinoma are types of esophageal cancer, one of the most aggressive malignant diseases. Since both histological types present entirely different diseases with different epidemiology, pathogenesis and tumor biology, separate therapeutic strategies should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), alternative strategies are actively sought to reduce the frequency of post-operative local or distant disease recurrence. Such strategies are particularly sought in the preoperative setting. Currently, the optimal management of resectable ESCC differs widely between Western and Asian countries (such as Japan). While Western countries focus on neoadjuvant or definitive chemoradiotherapy, neoadjuvant chemotherapy followed by surgery is the standard treatment in Japan. Importantly, each country and region has established its own therapeutic strategy from the results of local randomized control trials. This review discusses the current knowledge, available data and information regarding neoadjuvant treatment for operable ESCC.     

Postoperative split course radiotherapy of squamous cell carcinoma of the oral tongue.

Forty nine patients with squamous cell carcinoma of the oral tongue were irradiated postoperatively using a split course technique for external irradiation alone or in combination with intraoral cone X-ray therapy. After a 3 year follow-up the results of local control were compared with those of other authors, who irradiated initially with combined external and interstitial therapy in one series. For two series the nominal standard dose (NSD) was calculated with the modified Ellis formula given by Gabriel-Jurgens et al.¹⁰ and Gremmel et al.¹¹ In our patient collective the recurrence rate was higher in the early T-stages, because the dosage applied was lower than in the majority of the cited publications. The combined modality of surgery and following external irradiation could not improve the outstanding results of interstitial therapy in T1 and T2 tumors.When the split course technique is used, the total dose and treatment time must be increased to obtain the same local control rate as in one series irradiation. Especially in advanced cases the split dose regimen seems to be an alternative treatment, because severe complications were not observed in our patients. For split course therapy we recommend the application of 1700 ret for Stage T1 oral tongue carcinoma 1800 ret for Stage T2 and 1900 ret for T3 tumors. For treatment of recurrences, surgery appears to be superior to irradiation.     

The failure patterns of oral cavity squamous cell carcinoma after intensity-modulated radiotherapy-the university of iowa experience

PURPOSE: Determine the failure patterns of oral cavity squamous cell carcinoma (SCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between May 2001 and July 2005, 55 patients with oral cavity SCC were treated with IMRT for curative intent. Forty-nine received postoperative IMRT, 5 definitive IMRT, and 1 neoadjuvant. Three target volumes were defined (clinical target CTV1, CTV2, and CTV3). The failure patterns were determined by coregistration or comparison of the treatment planning computed tomography to the images obtained at the time of recurrence. RESULTS: The median follow-up for all patients was 17.1 months (range, 0.27-59.3 months). The median follow-up for living patients was 23.9 months (range, 9.3-59.3 months). Nine patients had locoregional failures: 4 local failures only, 2 regional failures only, and 3 had both local and regional failures. Five patients failed distantly; of these, 3 also had locoregional failures. The 2-year overall survival, disease-specific survival, local recurrence-free survival, locoregional recurrence-free survival, and distant disease-free survival was 68%, 74%, 85%, 82%, and 89%, respectively. The median time from treatment completion to locoregional recurrence was 4.1 months (range, 3.0-12.1 months). Except for 1 patient who failed in contralateral lower neck outside the radiation field, all failed in areas that had received a high dose of radiation. The locoregional control is strongly correlated with extracapsular extension. CONCLUSIONS: Intensity-modulated RT is effective for oral cavity SCC. Most failures are in-field failures. Further clinical studies are necessary to improve the outcomes of patients with high-risk features, particularly for those with extracapsular extension.     

Adenoendocrine cell carcinoma of the gallbladder clinically mimicking squamous cell carcinoma

We present the case of a 62-year-old Japanese man whose histological diagnosis was adenoendocrine cell carcinoma of the gallbladder at autopsy, but whose antemortem diagnosis was squamous cell carcinoma. The patient was admitted to hospital with complaints of occasional vomiting and abdominal pain. Abdominal computed tomography revealed a large tumor on the gallbladder involving the adjacent liver, colon, and duodenum, with multiple metastases in the greater omentum and paraportal lymph nodes. The serum level of squamous cell carcinoma antigen (SCCA) was high, whereas that of carbohydrate antigen (CA) 19-9, as well as that of carcinoembryonic antigen (CEA) was within the normal range. Due to these clinical features, we first suspected advanced squamous cell carcinoma of the gallbladder. After two cycles of gemcitabine monotherapy, the tumor had become enlarged and the regimen was changed to a combination of docetaxel and cisplatin. Though tumor regression was achieved and his serum SCCA level normalized after 3 months, the patient rejected additional chemotherapy and died 8 months after the diagnosis. The histopathological findings made by autopsy demonstrated the tumor to be an adenoendocrine cell carcinoma without squamous carcinoma cells. The case is interesting in that the clinical features were similar to those of squamous cell carcinoma of the gallbladder.     

Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer-related mortality worldwide. Although the utility of noninvasive biomarkers based on circulating cell-free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre- and postsurgery plasma samples will reveal OCSCC-specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor-specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head-neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma-derived cfDNA was analyzed by cfMBD-seq, which is a high-sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC-specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma-based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome-wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA-based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.     

Association between the diagnosis-to-treatment interval and overall survival in Taiwanese patients with oral cavity squamous cell carcinoma

BackgroundTo investigate the association between the diagnosis-to-treatment interval (DTI) and overall survival (OS) in patients with oral cavity squamous cell carcinoma (OSCC).MethodsA total of 18,677 patients with first primary OSCC identified in the Taiwanese Cancer Registry Database between 2004 and 2010 were examined. The effect of DTI on 5-year OS rates was investigated with multivariate Cox regression analysis. After the identification of the optimal cutoff for DTI based on the 5-year OS rates, DTI was classified in the following 20-day groups: ≤20 days (57% of the study patients), 21–45 days (34%), 46–90 days (6%) and ≥91 days (3%). In additional exploratory analyses, DTI was reclassified in the following 30-day interval groups: ≤30 days (81% of the study patients), 31–60 days (14%), 61–90 days (2%) and ≥91 days (3%).ResultsMultivariate analyses identified DTI (≤20 days versus other subgroups), sex (female versus male), age (<65 versus ≥65 years), clinical stage (p-stage I versus p-stage II, III, IV) and treatment modality (initial surgery versus initial non-surgery) as independent prognostic factors for 5-year OS. Compared with a DTI ≤20 days, the DTI categories ≥91 days (hazard ratio [HR]: 1.28, P < 0.001), 46–90 days (HR: 1.25, P < 0.001) and 21–45 days (HR: 1.07, P = 0.007) were independently associated with a higher risk of 5-year mortality. Similar results were obtained for DTI ≤30 days groups.ConclusionsDTI is independently associated with 5-year OS in OSCC patients. A DTI longer than 30 days or even 20 days may potentially decrease survival.