Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our departement from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I–III, I–IV, 210 II–IV, II–V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1–180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.     

头颈部鳞癌及癌旁组织端粒酶活性检测

目的：研究原发头颈部鳞癌及相关癌旁组织中端粒酶活性表达,探讨春作为头颈部鳞癌分子生物学标志物的可能性。方法：采用ＴＲＡＰ－ＰＣＲ－ＥＬＩＳＡ,对３２例原发头颈部鳞癌及１５例癌旁组织进行端粒酶活性检测。结果：３２例原发头颈部鳞癌中,２７例端粒酶活化,阳性率为８４．４％;１５例癌旁组织中５例端粒酶活化,阳性率为３３．３％。有淋巴结累及者端粒酶阳性率（８６．７％）高于无淋巴结累及者（８２．４％）,低分化     

Cancer stem cells in head and neck squamous cell carcinoma

Recent studies have demonstrated that cancer stem cells (CSC) play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). This subpopulation of undifferentiated, self-renewing cells is responsible for resistance to conventional anti-cancer therapy, cancer recurrence, metastasis and ability to form a heterogeneous tumor. CSC are identified on the basis of specific markers, including membrane proteins or cell enzymes, or by using their self-renewal properties. As their resistance to standard HNSCC treatment may eventually lead to the lack of treatment success, there is an urgent need to better understanding CSC biology and identify them as potential target new treatment modality.     

In vitro T-lymphocyte function in head and neck cancer patients

T-lymphocyte cell function was studied in vitro in peripheral blood mononuclear cells (PBMC) from 61 male patients with head and neck squamous cell carcinomas compared to 46 control patients. Patients older than 80 years or with reduced tumor-related performance status as measured by Karnofsky score less than 75 were excluded. In contrast to previous similar studies, control subjects ensured a minimum stress load by sampling all patients on the day of either diagnostic or therapeutic surgery. PBMC were separated by density-gradient centrifugation and subsequently cultured with autologous sera in vitro. The mitogen concanavalin A (Con A), which stimulates all T-cell clones, was employed. Findings showed that increased Con A stimulation and PBMC proliferation occurred with PBMC from cancer patients compared to that from control patients. In contrast, no differences could be detected with respect to the stimulated supernatant level of interleukin-2, interleukin-4 or interferon-γ between the groups. These results suggest that T-lymphocytes from PBMC are generally affected by neoplastic disease through either a supporting cell or serum factor.     

头颈部鳞癌端粒酶活性的定量检测

目的：了解头颈部鳞癌及其颈淋巴结转移癌端粒酶的表达情况,探讨粒酶活性定量分析在头颈鳞癌诊断中的价值。方法：采用端粒重复序列液体闪烁计数法检测端粒酶活性。共检测取自２５例头颈部鳞癌患者的组织样本５５份,其中７例患者同时取有原发癌及其颈淋巴结转移癌两份样本,以２３份正常组织为对照。结果：①３２份原发鳞癌组织中端粒酶活性（ｃｐｍ值）在１０００以上的２８份,除２份外,均明显高于正常组织;２３份正常组织的端     

Radiosensitization of advanced squamous cell carcinoma of the head and neck with cisplatin during concomitant radiation therapy

Treatment regimens for advanced squamous cell carcinoma of the head and neck require both attention to local tumor burden as well as contingencies for control of disseminated disease. Relatively new protocols utilizing cisplatin for radiosensitization of tumor cells during concomitant radiotherapy have shown progress in providing effective tumor control. Cisplatin as a chemotherapeutic agent induces DNA changes in malignant cells that may be mutagenic or lethal. Additionally, when used concurrently with radiation therapy, cisplatin acts as a radiosensitizer, increasing damage to malignant nuclear DNA to enhance the anti-neoplastic capability of radiotherapy. The mechanisms by which this radiosensitization occurs remain controversial, although one leading theory involves cisplatin’s ability to inhibit sublethal damage repair in radiated tumor cells. Recent investigations utilizing cisplatin with concurrent radiation for treatment of advanced squamous cell carcinomas of the head and neck are reviewed. The variations in protocols presented include route of administration, dosing, scheduling, timing with surgery, and combination therapy with 5-fluorouracil and radiation. Higher response rates, prolonged mean survival, increased survival rates, longer local recurrence-free survival rates, and considerable organ preservation with the use of concurrent cisplatin and radiation have been demonstrated by these studies. Further investigation of concurrent cisplatin and radiotherapy in patients with advanced disease is justified. Received: 5 March 1999 / Accepted: 15 March 1999     

Current applications of microarrays in head and neck cancer research

OBJECTIVES/HYPOTHESIS: The objective was to introduce microarray technology and its applications in cancer research to the head and neck clinician. STUDY DESIGN: Literature review combined with methodology and examples from the authors' experiences with microarray analysis of tumors of the head and neck. METHODS: Search of literature and the authors' experience was made for technical details, alternative methods of data analysis, available bioinformatics tools, and applications of microarrays in cancer research. RESULTS: Microarrays allow the simultaneous analysis of the expression of thousands of genes. The use of a well-developed microarray study design leads to informative results. There are various bioinformatics resources widely available to aid in the analysis of microarray data. However, there is not yet a gold standard for analysis because this methodology is still evolving. CONCLUSION: Microarray studies may allow researchers to identify genetic changes relevant to diagnosis and prognosis in patients with head and neck cancer. Although still relatively new, this powerful methodology has immense potential to aid in understanding of the genetic changes that are important in head and neck cancer.     

Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck region

Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.     

Comparison between PET and PET/CT in recurrent head and neck cancer and clinical implications

The aim of this retrospective study was to compare the diagnostic accuracy between positron emission tomography (PET) and combined PET/computed tomography (PET/CT) in the detection of recurrent head and neck squamous cell carcinoma (HNSCC) and to evaluate the degree of interobserver agreement. Thirty-two patients who had undergone curative treatment for HNSCC and who presented with a suspicion of recurrent local disease were studied with fluoro-2-deoxy-D-glucose (FDG)-PET imaging. All patients had undergone an inconclusive conventional workup (nasofibroscopy, CT scan and/or MRI). PET and PET/CT were reviewed by two nuclear medicine physicians independently. Performances of PET and PET/CT were compared using biopsy and/or clinical follow-up of at least 8 months as gold-standard. ROC curves were employed for statistical analysis. Out of 32 patients, 18 (56%) had a local recurrence. Intraclass correlation coefficients were strong (>90) and statistically significant (P < 0.0001) for the two reviewers in all cases. The sensitivity, specificity and accuracy of PET were found to be 94%, between 36 and 50% and between 69 and 75%, respectively, depending on the consideration of equivocal cases. Results for PET/CT were found to be 94, 57 and 78%. The utility scores of PET and PET/CT were 0.72 and 0.78, respectively. PET/CT could have a direct impact on patient care with the avoidance of 8/14 (57%) unnecessary invasive procedures (panendoscopy under general anaesthesia). Combined PET/CT is more accurate than PET alone for detection of recurrent HNSCC. The findings of this study are reinforced by the strong interobserver agreement in the interpretation of the results.     

Genomic screening of head and neck cancer and its implications for therapy planning

Despite great technical improvements in radiotherapy and surgery, survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has still not improved significantly over the last decades. Management of SCCHN has mainly been based on the TNM staging and site over this time period, even though we know that there are individual differences independent of the TNM status. Individual patients with small tumors might have a poor outcome, and patients with large tumors may end up with a favorable prognosis, despite their respective TNM classification. Recent molecular studies indicate that underlying genetic abnormalities may reflect such individual differences independently of TNM status. Individualization of treatment based on such biological properties of the tumors might result in less over as well as under treatment. However, the optimal panel of biomarkers to be used for the individualization of treatment is yet to be defined. A variety of laboratory techniques have been used in studies that investigate the individual biological features, spanning from methods that screen the genome for chromosomal and genetic abnormalities, e.g., cytogenetics, CGH, SKY and cDNA micro array, to detailed studies of specific aberrations. The purpose of this review of the literature is to summarize what has been studied so far by methods for genetic screening and to relate these results to the prediction of the clinical outcome. We conclude that it is time to focus future prospective studies on how treatment can be individualized based on biomarkers in combination with the macroscopic features of SCCHN.     

Characterization of FaDu-R,a radioresistant head and neck cancer cell line,and cancer stem cells

Objectives

The aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC.

Oncogens in ENT and head and neck — a review

With the exploration of new horizons in the frontiers of genetic linkage with head and neck cancer by advanced molecular biological technique it may be possible to know the various steps involved in the cancer development and new prognostic markers for not only predicting prognosis but also progression and predisposition including routine diagnostic tests for mutantgenes for a better diagnosis and treatment of squamous cell cancers of head and neck. Various oncogens and their products so far identified are ras, myc, c-erb, Bl, PRAD-.l, int-2, hst-1 and p 53 etc with lirikage to head and neck malignancy. The HLA gene association is the most convincing evidence for the role of genetics in the aetiology of nasopharyngeal cancer. EGFR looks to be a promising prognostic indicator as its interaction with the polypeptide epidermal growth factor stimulates proliferation of target cells.     

Current perspectives in the use of monoclonal antibodies for detection and treatment of head and neck tumors

Squamous cell carcinomas (SCC) represent the vast majority of all malignant tumors of the head and neck. The development of distant metastases is now more often observed among these tumors than in the past. The department of Otolaryngology-Head and Neck Surgery, Free University Hospital has focussed upon the use of monoclonal antibodies (mAb) for treating SCC metastases. MAb E 48 was selected after it was shown to react strongly to SCC and minimally to normal tissues. In animal models clear tumor visualization and impressive tumor regression occurred when the antibody was linked to a suitable isotope. A diagnostic phase I/II study for the detection of lymph node metastases has entered 51 patients with head and neck cancer. Biodistribution data, acquired from surgical specimens, has shown an average tumor uptake of 30m%/g tumor tissue of the injected dose of mAb E 48. Extrapolation of data from therapeutic animal studies to these findings suggests that radioimmunotherapy can be effective in head and neck cancer patients, notably as adjuvant therapy in patients with a high chance of developing distant metastases.Part of this research was supported by Centocor BV, Leiden, The Netherlands, the Dutch Ministry of Economic Affairs and the Dutch Cancer Foundation     

Proteolytic patterns of head and neck squamous cell carcinoma

The significance of plasminogen activators and matrix metalloproteases for clinical outcome, growth and metastatic behavior of head and neck squamous cell carcinoma (SCC) is still controversial. The majority of studies has been based on either immunohistological stainings, which provide only limited quantitative information, or in vitro experiments. We analyzed 44 head and neck SCC and 11 mucosa tissue samples for the expression of gelatinolytic or fibrinolytic proteases by quantitative zymographic analysis and compared lytic activities to clinical and histopathological data. We calculated activation ratios for matrix metalloproteinases-2 and –9 (MMP-2 and MMP-9) by separate evaluations of inactive and activated MMP forms. Increased gelatinolytic and fibrinolytic activity was found in head and neck SCC when compared to mucosa. Increased values were caused by MMP-9 and urokinase type plasminogen activator, respectively. No statistically significant correlations of either protease lytic activity or activation ratio could be related to T-stage, metastasis, tissue necrosis or the differentiation stage of tumors. The data recorded are compared with previously published reports. Received: 27 August 1998 / Accepted: 6 January 1999     

Radiotherapy in N0 head and neck cancer patients

Summary The efficacy of elective radiotherapy in N0 cancer of the oropharynx, hypopharynx and supraglottic larynx was assessed retrospectively in a large series of head and neck cancer patients treated at the Institut Curie between 1958 and 1976. Despite a significant incidence of false-negative cases accompanied by extracapsular tumor spread, radiation tissue doses of 4500–5500 cGy were highly successful in preventing nodal disease in clinically negative necks. Isolated node failure occurred in only 2% of 611 cases of oropharyngeal and pharyngolaryngeal cancer from a total group of 1646 patients and 2% of 237 N0 cases of supraglottic vestibular cancer taken from a series of 340 patients. The impact of neck status on survival and disease-free survival is discussed. Present findings show that elective irradiation of the neck is easily integrated into the radiation management of primary pharyngeal and supraglottic laryngeal cancers and results in no additional morbidity to patients so treated.Presented at the International Symposium: Diagnosis and treatment of the N0 neck of carcinomas of the upper aero-digestive tract, 18 September 1992, Göttingen, Germany     

Efficacy of fluoro-2-deoxy-D-glucose positron emission tomography to evaluate responses to concurrent chemoradiotherapy for head and neck squamous cell carcinoma

Objective

This study evaluates the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with head and neck squamous cell carcinoma (HNSCC) who received concurrent chemoradiotherapy (CCRT).

Methods

Sixty-five patients were recruited for this study between November 2002 and April 2007. The FDG-PET scan was performed before treatment and 4–6 weeks after treatment.

Results

The mean of maximum standardized uptake value (SUVmax) before treatment at the primary tumor site was 8.1 (range, 2–22). The sensitivity of FDG-PET for the diagnosis of primary tumor site was 98%. The mean of SUVmax after treatment was 2.6 (range, 2–5). The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of primary tumor site after treatment were 100%, 40%, and 46%, respectively.The mean of SUVmax before treatment at the nodal site was 4.7 (range, 2–16). The mean of SUVmax after treatment was 2.0 (range, 2–6.7). The pre-treatment SUVmax of T2, T3, and T4 stages were significantly higher than that of the T1 stage. The N stage had no correlation in terms of the pre-treatment nodal site SUVmax.

Conclusion

Our results indicate that FDG-PET is a useful imaging method for evaluating the response of CCRT in patients with HNSCC. However, performing FDG-PET 4–6 weeks after treatment may be too early as it may give false-positive results due to fibrosis and scarring.     

头颈部肿瘤DNA的定量分析

目的：探讨细胞定量学分析在诊断头颈部肿瘤中的意义。方法：应用全自动细胞图像分析仪测定23例头颈部恶性肿瘤和20例良性病变患者的细胞核DNA指数(DI)、S期细胞分数(SPF)、细胞增殖指数(PI)和DNA大于5c的核的比率(5c Ex)。结果：细胞定量分析和常规细胞学检查的阳性率分别为76．92％和50．00％，SPF、PI和5c Ex在恶性病变组分别为14，05％、19.59％和1．59％，SPF和PI在肿瘤部位的细胞增生程度高，与瘤旁1cm和手术切缘处存在明显不同。结论：全自动细胞图像分析仪的细胞定量诊断阳性率较常规细胞学检查明显提高，异倍体率、SPF、PI和5c Ex指标在诊断头颈部肿瘤、估计肿瘤的生物学恶性程度和评估手术范围等临床工作中有一定参考价值。     

Synchronous laryngeal squamous cell carcinoma and Hodgkin lymphoma of the head and neck region

During the pathologic examination of neck dissection specimens, unexpected findings may occasionally be encountered. Such findings include the presence of a second primary tumor or a chronic infectious or inflammatory disease. We report a case of a 65-year-old man who underwent a supracricoid partial laryngectomy and bilateral neck dissection for squamous cell carcinoma of the larynx. Histopathologic examination of the larynx revealed well-differentiated squamous cell carcinoma, but examination of the neck dissection specimen revealed a mixed cellularity subtype of classical Hodgkin lymphoma.     

Selective neck dissection for the treatment of neck metastasis from squamous cell carcinoma of the head and neck

OBJECTIVE: Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. STUDY DESIGN: A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. METHODS: A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20-85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1-64 mo). Twenty-six patients had clinically negative (cNo) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. RESULTS: Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patientswere surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). CONCLUSIONS: With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.