Oral verrucous carcinoma. Treatment with radiotherapy

Fifty-two cases of oral verrucous carcinoma treated with radiotherapy at the Regional Cancer Centre, Trivandrum, Kerala, India in 1982 were evaluated to determine the distribution within the oral cavity, clinical extent, and effectiveness of radiotherapy in controlling the disease. The most common site was the buccal mucosa. Fifty percent of the patients had clinically negative regional lymph nodes and 33% were in earlier stages (T1, T2, N0, and M0). The overall 3-year no evidence of disease (NED) survival rate was 44%. The 3-year NED survival rate with radium implant was 86%. We cannot comment on anaplastic transformation after radiotherapy because our treatment failures have not been subjected for biopsy concerning this matter. Because the results are comparable with those of well-differentiated squamous cell carcinoma, we think that the treatment policies advocated for oral squamous cell carcinoma are also applicable to oral verrucous carcinoma.     

Proliferative verrucous leukoplakia and its related lesions

Proliferative verrucous leukoplakia (PVL) is a unique type of clinical oral leukoplakia. Enigmatic in etiology, PVL behaves in a far more aggressive fashion than other forms of leukoplakia. Its aggressiveness relates not only to a high recurrence rate, but more so to a very high level of and relentless progression from a localized simple keratosis to extensive oral disease and squamous carcinomas of verrucous, or conventional squamous cell type. Diagnosis is often late in the protracted course of PVL with the disease in an advanced stage when it is especially refractory to treatment. Within the histologic spectrum that is seen in PVL, usually as a function of time, are: (1) verrucous hyperplasia (VH), a histologically defined lesion; (2) varying degrees of dysplasia; and (3) three forms of squamous cell carcinoma: verrucous, conventional and, according to some, papillary squamous cell carcinoma. Each of these are discussed both within and outside the context of PVL. VH is a forerunner of verrucous carcinoma and the transition is so consistent that the hyperplasia, once diagnosed, should be treated like verrucous carcinoma. VH is not only an oral lesion; it can occur in the upper airway (sinonasal tract and larynx) where it is not usually found within a maternal soil of PVL. Papillary squamous cell carcinoma has been a loosely defined neoplasm, more often considered a verrucal type of malignancy. It nonetheless is a distinct clinicopathologic entity, separate from verrucous carcinoma and without a predilection for the oral cavity or an association with PVL.     

High-resolution DNA flow cytometry in oral verrucous carcinoma

The classification of verrucous carcinoma as an entity unto itself or as a variant of well differentiated squamous cell carcinoma is controversial. To contribute new insights into the biological behavior of this rare tumor, we applied DNA flow cytometry to three node-negative verrucous carcinomas of the oral cavity. All tumors expressed a single aneuploid cell population. One of the patients experienced three courses with local recurrence. All secondary tumors retained the initially established aneuploid clone. The development of aneuploidy is thus a cytogenetic event common to both verrucous and squamous carcinoma of the oral cavity.     

Pathological and clinical analysis of 102 cases of lip carcinoma

102 cases (103 tumors) of lip carcinoma treated by surgery are analyzed. There were 37 (35.9%) verrucous carcinoma and 66 (64.1%) squamous cell carcinoma which included grade I 29 cases, grade II 21, grade III 14 and grade IV 2. Of the 66 squamous cell carcinomas, six lesions co-existing with verrucous carcinoma were derived from the latter. This fact demonstrated that anaplastic transformation of verrucous carcinoma could occur in patients without radiotherapy. This study suggests that the enlarged neck lymph nodes need not be dissected prophylactically for patients with squamous cell carcinoma grade I and grade II, and with verrucous carcinoma. The management of the cervical nodes still suffices if they enlarge after the primary lesion has been removed. But radical dissection of neck lymph nodes should be performed promptly for patients with squamous cell carcinoma grade III and grade IV.     

Squamous cell carcinoma of the oral cavity in young adults

The 12 patients less than 35 years of age treated for squamous cell carcinoma of the oral cavity at the American Oncologic Hospital between 1954-1979 are examined. Group A (eight patients) had involvement of the tongue; Group B (4 patients) had carcinoma of other oral sites. Mean “T” stage for Group A and Group B was 1 and 1.5, respectively. Treatment was surgical in the majority of cases. Seventy-one percent of Group A and 25% of Group B developed metastatic disease to the neck. The 2-year survival rate was 57% (A) and 75% (B) — 75% combined. The collective results of this and other studies suggest lower control rates than those reported for older patients with similar initial presentations. The implications of this observation are discussed in relation to the management of the younger patient with squamous cell carcinoma of the oral cavity.     

Comparison between conventional and intensity-modulated post-operative radiotherapy for stage III and IV oral cavity cancer in terms of treatment results and toxicity

The aim of this study was to assess the treatment results and toxicity profiles of post-operative conventional radiotherapy (Conv-RT) and intensity-modulated radiotherapy (IMRT) for stage III and IV oral cavity cancer. During the period from April 2002 to December 2005, a total of 49 patients with stage III and IV squamous cell carcinoma of the oral cavity were treated with radical surgery followed by post-operative RT. Twenty-seven patients received Conv-RT while 22 received IMRT. Only three patients received adjuvant chemotherapy. With a median follow-up time of 3.3 years, the 3-year overall survival and disease-free survival rates for patients who received Conv-RT vs IMRT were comparable. There was no significant difference in acute toxicity between the two different RT techniques. However, in terms of late toxicity, patients receiving IMRT had significantly less moderate to severe xerostomia and dysphagia than those receiving Conv-RT (36% vs 82%, p=0.01 for xerostomia and 21% vs 59%, p=0.02 for dysphagia). Post-operative Conv-RT and IMRT are equally effective in terms of tumor control for locally advanced oral cavity cancer. Patients receiving IMRT had comparable acute and significant less late toxicity than those receiving Conv-RT.     

Treatment results of oral verrucous carcinoma and its biological behavior

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.     

60例上皮源性鼻腔癌的临床疗效分析

目的：评价上皮源性鼻腔癌的临床疗效及影响预后的因素。方法：回顾性分析1995－1992年收治的60例上皮源性鼻腔癌。其中单纯放射治疗34例,手术＋放射治疗26例。生存统计采用Kaplan-Meier法,组间比较采用Log-rank检验,多因素分析采用Cox模型。结果：总5年生存率为55．9％,10年生存率为36．9％。早期患者（I、Ⅱ期）的5,10年生存率分别为79．0％和57．9％,晚期患者（Ⅲ、Ⅳ期）的5,10年生存率则分别为44．1％和26．0％,二者差异有显著性（P＝0.005)。手术＋放射治疗与单纯放疗的生存率差异无显著性（P＝0．33）,鳞癌的生存率明显低于腺癌（P＝0．04）,初诊时颈部有淋巴结转移者的5,10年生存率低于无颈部淋巴结转移者（P＝0.09).结论:治疗方式`颈部淋巴结转移对预后无明显影响,而病理类型`临床分期对预后有显著影响.     

Advanced squamous cell carcinoma of the base of the tongue treated with surgery and post-operative radiotherapy.

BACKGROUND: Early stage squamous cell carcinoma of the base of the tongue has been successfully treated with radiotherapy and brachytherapy. However, the vast majority of these tumours seen in Western Europe are already at an advanced stage. Medical records of 79 patients with squamous cell carcinoma of the base of the tongue treated between 1980 and 1994 were examined. METHODS: Eighty-three per cent of the primary tumours were stage T3 or T4. Fifty-nine patients were treated with surgery and post-operative radiotherapy. Quality of life assessment amongst the survivors was performed by means of a questionnaire. RESULTS: Five year disease free survival in patients undergoing excision for T3-T4 tumours was 59%. Patients with T2-T3 tumours undergoing partial excision of the tongue base had a 3 year recurrence free survival rate of 68%. Distant metastasis occurred in 16%. Seventy-eight per cent of the patients judged their quality of life to be near normal. CONCLUSION: Surgery and post-operative radiotherapy offer a reasonably good survival in advanced carcinoma of the base of the tongue with preservation of quality of life.     

Predictive factors for distant metastasis from oral and oropharyngeal squamous cell carcinoma

The presence of distant metastasis after the initial treatment of head and neck squamous cell carcinoma is not considered a common event and is associated with a poor outcome. The objective of this study was to investigate the prevalence and risk factors associated with the diagnosis of distant metastasis in oral and oropharyngeal carcinoma patients. The medical charts of 2327 patients treated from 1954 to 1997 were reviewed. They were 1703 patients (73.2%) with oral cavity and 624 (26.8%), oropharyngeal tumours. Regarding the primary treatment: 637 patients (27.4%) underwent surgery alone; 1147 (49.3%), radiotherapy alone and 543 (23.3%), combined treatment (surgery and radiotherapy). During the follow-up period after the initial treatment, 89 patients (3.8%) were diagnosed with distant metastasis. The variables associated with the distant metastasis-free survival were: tumour site (p=0.008); T stage (p<0.001); N stage (p<0.001); treatment performed (p<0.001) and decade of admission at the institution (p<0.001). The multivariate analysis (Cox regression) showed that the clinical stage (p=0.007); treatment performed (p=0.012) and decade of admission at the institution (p=0.004) were independent predictive factors for distant metastasis. Distant metastasis has been diagnosed more frequently in the latter decade and the significant predictors associated with its presence were the advanced clinical stage and patients who had undergone combined treatment.     

肛管癌的疗效和预后因素分析

目的 回顾分析原发性肛管癌患者的疗效和预后因素。方法 2000—2011年本中心经治肛管癌患者3l例,鳞癌23例、腺癌8例。Ⅰ~Ⅲ期患者首程采用放疗为主治疗16例、手术为主治疗11例、化疗3例。结果 随访率为90%,随访时间满3年的样本数21例。全组3年总生存(OS)率和无进展生存(PFS)率分别为76%、56%。单因素分析显示临床分期和T分期为OS预后因素(χ²=12.11,P=0.001和χ²=4.64,P=0.031),并与PFS有相关趋势(χ²=2.91,P=0.088和χ²=2.75,P=0.097)。Ⅰ~Ⅲ期鳞癌患者首程放疗为主与手术为主治疗的3年OS率和PFS率均相似(80%与80%,χ²=0.08,P=0.776和78%与67%,χ²=0.17,P=0.697)。放疗患者3级皮肤或黏膜急性不良反应为37%,晚期肛门感觉或功能异常为9%。结论 临床分期、T分期是影响肛管癌患者预后的最主要因素,同期放化疗应作为肛管鳞癌患者根治性治疗手段的首选疗法,应用调强放疗技术有利于患者按计划完成放疗并避免发生严重不良反应。     

Recurrence and salvage treatment of squamous cell carcinoma of the oral cavity

The aim of this study was to evaluate the incidence and predictive factors for recurrence of oral squamous cell carcinoma (SCC) and outcome according to salvage treatment modality. A retrospective analysis of 127 oral cavity cancer patients who underwent surgery with or without postoperative radiotherapy as initial treatment was performed. Thirty-six patients (28%) were observed with recurrences and/or metastases mostly at the primary site and neck. Seventy-eight percent of recurrences occurred within one year, and 92% within two years after the initial treatment. The rate of recurrence and/or metastases was significantly higher in patients with an advanced pathologic stage, pathologic lymph node and positive resection margin compared to those with an early pathologic stage, negative lymph node and negative resection margin (p<0.05). Especially, regarding the relationship between the rate of locoregional recurrence and local or regional factors, resection margin status was a particularly important, and potentially preventable, independent predictor for locoregional control. Patients who underwent salvage surgery with or without postoperative radiotherapy had significantly improved salvage and total survival times compared with patients who received chemotherapy and/or radiation therapy for their recurrence.     

Prognosis and clinicopathological characteristics of Ib-IIb adenocarcinoma of the uterine cervix in patients who have had radical hysterectomy.

AIMS: The aim of the present study was to evaluate the outcome of patients with stage lb-IIb cervical adenocarcinoma treated with radical hysterectomy, and to determine the clinicopathological characteristics of those patients. METHODS: A total of 255 patients with cervical carcinoma stage Ib-IIb (57 adenocarcinoma and 198 squamous cell carcinoma) who had undergone radical hysterectomy were included in this study. Patient survival distribution was calculated using the Kaplan-Meier method. RESULTS: The estimated 5-year survival rate for patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma (77.9% vs 91.7%). The survival rate in stage Ib patients did not differ between two groups (95.8% vs 94.4% respectively). The incidence of lymph node involvement was significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma (31.6% vs 14.8%). Among patients receiving post-operative radiotherapy, the survival rate for adenocarcinoma (71.1%) was significantly poorer than that for squamous cell carcinoma (90.0%). When patients underwent radical hysterectomy, the survival rate for stage II patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma. CONCLUSIONS: The higher incidence of lymph node involvement and lower response to post-operative radiotherapy are considered to be factors of poorer prognosis in cervical adenocarcinoma.     

National survey of head and neck verrucous carcinoma: patterns of presentation, care, and outcome.

BACKGROUND: Verrucous carcinoma is distinguished by controversy regarding appropriate diagnosis and treatment. This study provides a contemporary survey of demographics, patterns of care, and outcome for this disease in the United States. METHODS: The National Cancer Data Base had 2350 cases of verrucous carcinoma of the head and neck diagnosed between 1985 and 1996. Statistical procedures included chi-square analyses, Student t tests, and relative survival. RESULTS: Tumors originated most frequently in the oral cavity (55.9%) and larynx (35.2%). Although most patients were male (60.0%), oral cavity tumors were more common among older females. The most prevalent treatment was surgery alone (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation alone (10.3%). For oral cavity tumors, surgery alone was more common among early (85.8%) than advanced cases (56.9%); a larger proportion of advanced disease received radiation alone or surgery and irradiation combined. Most laryngeal tumors were treated with surgery (60.3% for early and 55.6% for advanced disease), but a higher proportion received radiation alone or surgery combined with radiation compared with oral cavity cases. Five-year relative survival was 77.9%. For localized disease, survival after surgery was 88.9% compared with 57.6% after irradiation. CONCLUSIONS: Demographic differences implicate different mechanisms of carcinogenesis for verrucous carcinoma arising in the oral cavity and the larynx. Although selection bias may account for the differences observed, patients receiving initial treatment with surgery had better survival than those treated with irradiation, especially for cases originating in the oral cavity.     

Squamous Cell Carcinoma of the Oral Cavity: An unselected material from a 5-year period

Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. Two per cent received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine per cent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors.     

The clinical significance of pathological findings in surgically resected margins of the primary tumor in head and neck carcinoma

Two hundred seventy (270) consecutive surgical patients treated at Roswell Park Memorial Institute for carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx between 1977 and 1982 were reviewed to determine the relationship between pathological findings at the surgical margins of the primary tumor and the incidence of local recurrence and clinical outcome. The estimated 5-year disease-free survival rate was 39% for patients with free surgical margins (10%--hypopharynx, 30%--oropharynx, 40%--oral cavity, and 53%--larynx) and 7% for not-free surgical margins. Patients with free surgical margins and with well-differentiated squamous cell carcinoma had better prognosis than those patients with moderately- and poorly-differentiated carcinomas. The local recurrence rate for Stage T1 and T2 lesions with free surgical margins was 17%, compared with 27% for Stages T3 and T4. The results of this study indicate that pathological evidence of complete excision of the primary tumor is important and attempts should be made to obtain pathological clearance. The local recurrence rate for Stage T3 and T4 lesions is high. Adjuvant therapy is indicated and post-operative radiotherapy is recommended.     

Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial.

PURPOSE: Prognosis of patients with advanced oral cavity cancer is worth improving. Chemotherapy has been reported to be especially active in oral cavity tumors. Here we repeat the results of a randomized, multicenter trial enrolling patients with a resectable, stage T2-T4 (> 3 cm), N0-N2, M0 untreated, squamous cell carcinoma of the oral cavity. PATIENTS AND METHODS: Patients were randomly assigned to three cycles of cisplatin and fluorouracil followed by surgery (chemotherapy arm) or surgery alone (control arm). In both arms, postoperative radiotherapy was reserved to high-risk patients, and surgery was modulated depending on the tumor's closeness to the mandible. Patients' accrual was opened in 1989 and closed in 1999. It included 195 patients. Results: In the chemotherapy arm, three toxic deaths were recorded. No significant difference in overall survival was found. Five-year overall survival was, for both arms, 55%. Postoperative radiotherapy was administered in 33% of patients in the chemotherapy arm, versus 46% in the control arm. A mandible resection was performed in 52% of patients in the control arm, versus 31% in the chemotherapy arm. CONCLUSION: The addition of primary chemotherapy to standard surgery was unable to improve survival. However, in this study, primary chemotherapy seemed to play a role in reducing the number of patients who needed to undergo mandibulectomy and/or radiation therapy. Variations in the criteria used to select patients for these treatment options may make it difficult to generalize these results, but there appears to be room for using preoperative chemotherapy to spare destructive surgery or radiation therapy in patients with advanced, resectable oral cavity cancer.     

Cancer of the Nasal Cavity and Paranasal Sinuses: A Clinico-pathological Study of 277 Patients

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (NO 48% vs. Nl-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).     

Clinical outcome and tumour microenvironmental effects of accelerated radiotherapy with carbogen and nicotinamide

Experimental studies have shown an almost 2-fold increase in effectiveness if accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) was compared with standard radiotherapy. This combination was chosen in order to overcome repopulation of clonogens during radiotherapy and to minimize tumour hypoxia. Analysis of microenvironmental parameters is required to identify tumours that can benefit from these new treatment approaches. In this study 124 patients with stage III or IV head and neck squamous cell carcinomas received ARCON treatment. Vascular architecture, perfusion, proliferation and oxygenation were studied in two human laryngeal squamous cell carcinoma xenograft lines and the effects of carbogen and nicotinamide were analysed. Loco-regional control for stage III-IV larynx carcinomas was 85%, for hypopharynx carcinomas 50% and for oral cavity and oropharynx carcinomas 65%. In the experimental studies, carbogen treatment resulted in one tumour line in a decrease of blood perfusion, which was reversed if nicotinamide was added. The other tumour line showed no perfusion changes after carbogen or nicotinamide treatment. Both tumour lines showed a drastic reduction of hypoxia after carbogen breathing only or carbogen breathing plus nicotinamide. The ARCON schedule results in high loco-regional tumour control rates. Analysis of tumour microenvironmental parameters showed differences in response to carbogen and nicotinamide between different tumour lines of similar histology and site of origin. This indicates that it may be advantageous to base the selection of patients for oxygenation modifying treatment on microenvironmental tumour characteristics.     

Development of a new staging system for recurrent oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: Approximately 33% of patients with squamous cell carcinoma of the oral cavity and oropharynx develop a recurrence. The management of recurrent tumors can be challenging to both physician and patient, at least in part due to the lack of an accurate and clinically applicable staging system for these patients. The purposes of this study were to examine the survival patterns of patients presenting with recurrent oral cavity and oropharyngeal tumors, to identify key factors affecting prognosis, and to combine these factors to create a new staging system to predict survival and aid in planning therapy. METHODS: The methods included a retrospective chart review of 641 patients with oral cavity and oropharyngeal squamous cell carcinoma who underwent their initial treatment at Washington University between 1980 and 1992. From this population, 249 patients (39%) developed a recurrence. RESULTS: The overall 2-year survival rate was 20% (50 of 249 patients). Six variables affected survival significantly: histologic differentiation, initial (prior to first therapy) TNM stage, initial treatment, time to recurrence, extent of recurrence, and treatment of recurrence. These six variables were entered into a logistic model to determine the individual prognostic significance of each variable. Two variables were found to be statistically significant: initial TNM stage (chi-square test = 7.67; P = 0.0056) and extent of recurrence (chi-square test = 11.75; P = 0.0006). Using the process of conjunctive consolidation, these two variables were combined to create a new staging system for recurrent tumors of the oral cavity and oropharynx. CONCLUSIONS: This staging system provides accurate estimates of prognosis, involves no new technology to implement, demonstrates statistically significant differences in survival by stage, and may aid both the physician and the patient in planning therapy.