Efficacy of radiologic screening for distant metastases and second primaries in newly diagnosed patients with head and neck cancer

OBJECTIVES: Detection of distant metastases and second primary tumors in newly diagnosed patients with head and neck cancer has usually a major effect on prognosis but does not always influence clinical management. This must be considered when radiologic screening investigations are used. The present study particularly evaluates how often additional neoplastic lesions detected by screening had an impact on therapy. STUDY DESIGN: The authors conducted a single-institution retrospective analysis. METHODS: The medical records of 260 patients with newly diagnosed squamous cell carcinoma of the head and neck treated between 1999 and 2002 were retrospectively analyzed. Before therapy, all patients had undergone screening by computed tomography scan of the chest, abdominal ultrasound, and bone scintigraphy. RESULTS: Screening investigations identified 16 patients (6.2%) with distant metastases and six patients (2.3%) with simultaneous second primaries. Chest computed tomography scan detected 20 neoplastic lesions; abdominal ultrasound and bone scintigraphy each detected 2. Three findings of distant metastases proved to be false-positive during follow up. Of the 22 patients with positive screening results, clinical management was affected in 13 (59.1%). Twelve were originally scheduled for curative surgery and 10 had chest abnormalities. CONCLUSION: Chest computed tomography scan was the most effective screening investigation, which should be routinely used whenever curative surgery of head and neck cancer is planned. Abdominal ultrasound and bone scintigraphy may sometimes be valuable before extensive surgical treatment of far advanced disease. In patients scheduled for primary radiotherapy, radiologic screening had hardly any consequence and should be confined to conventional x-ray of the chest.     

Immunosuppressive retroviral-related factors in sera of patients with head and neck cancer

Summary The chemotactic responsiveness of mononuclear phagocytes has often been found defective in patients with various malignancies. We have previously reported a defective chemotactic responsiveness in patients with head and neck cancer. Low-molecular-weight factors (LMWFs) have been isolated from tumors and can be held responsible for the inhibitory effect on monocyte chemotactic responsiveness. It is an intriguing new finding that these LMWFs can be neutralized by antibodies reactive to P15E, a structural envelope protein of murine leukemia retroviruses. In this report we describe a relatively easy and rapid method for the detection of immunosuppressive P15E-like factors in the sera of patients with head and neck cancer. The test is based on the monocyte polarization assay. Although only nine head and neck cancer patients were included in this study, the findings indicate that the test might be of value for clinical application. An early detection of a recurrence after treatment might be possible by the finding of a reappearance of the P15E-like factors in patients' sera during follow-up.     

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     

Chest computerized tomography scanning in patients presenting with head and neck cancer

Between 1 to 16% of patients with head and neck squamous cell carcinoma (HNSCC) have synchronous tumours; the majority (>50%) occurring within the lung. Previous studies have relied upon endoscopy and chest radiographs. The aim of this study was to determine the incidence of synchronous intrapulmonary tumours in this group of patients using computerized tomography (CT) scanning. Over 36 months, 111 consecutive patients were assessed at presentation by contrast enhanced CT scanning from the skull base to the diaphragm. Chest scans showed intrapulmonary lesions in 17 patients and 10 have, with time, been confirmed as neoplastic. These allowed treatment of three primary bronchial carcinomas following radical treatment of the index tumour and cancellation of radical treatment in five patients with metastases. Two patients with possible metastases at presentation underwent radical treatment to the index tumour with subsequent follow-up confirming metastatic chest disease. All 10 patients eventually died of either locoregional or metastatic disease. This is one of the first prospective reports of chest scanning in patients with head and neck cancer. An additional chest scan in this group, many of whom undergo a staging scan of the neck, requires an extra 10 min with no further contrast and in this study yielded a synchronous tumour rate of 9%.     

The potential uses of high-dose-rate brachytherapy in patients with head and neck cancer

Brachytherapy has proven to be an extremely valuable method of treatment for head and neck cancer. The data supporting its application, however, is based on continuous low-dose-rate brachytherapy. To benefit from improved radiation protection, outpatient treatments, and increased patient tolerance of treatment set-up over that encountered in conventional low-dose-rate manually afterloaded brachytherapy, we implemented a high-dose-rate remote afterloading approach in selected patients with head and neck cancers. This treatment was utilized in two different roles in managing 29 patients. In its first role, it was used as the sole treatment in 13 patients with T1–2 NO malignancies. A total of ten treatments of 450–500 cGy each were delivered twice a day with a minimum of 5–6 h between treatments. With a median follow-up of 9 months, only 1 patient failed locally. In a second role, brachytherapy was applied in a post-operative adjuvant setting following wide local excision of tumors in patients who presented with recurrent disease (12 cases) or a second primary in the head and neck (4 cases). All patients had previously received external irradiation to the head and neck. Due to this previous course of irradiation, only eight treatments of 300 cGy each were delivered, for a total of 2400 cGy over a period of 4 days. However, with a follow-up of 2–16 months, only 3 patients remain disease-free.Presented at the combined meeting of the Society of Head and Neck Surgeons and the European Organization for Research and Treatment of Cancer, Paris, France, 25–28 May 1994     

Paraneoplastic syndromes in patients with primary head and neck cancer

Paraneoplastic syndromes represent the clinical manifestations of the indirect and remote effects produced by tumor metabolites or other products. The clinical spectrum of the various paraneoplastic syndromes related to primary malignancies of the head and neck region is presented. A review of the literature on paraneoplastic syndromes in patients with primary head and neck cancer was carried out. Paraneoplastic syndromes related to primary malignancies of the head and neck region can be categorized as: endocrine, cutaneous or dermatologic, hematologic, neurologic, osteoarticular or rheumatologic, ocular syndromes. Sometimes, paraneoplastic syndromes can be more serious than the consequences of the primary tumor itself and can precede, follow or be concurrent to the diagnosis of a malignancy; moreover, they can dominate the clinical picture and thus lead to errors with respect to the origin and type of the primary tumor. Physicians who deal with cancer-associated syndromes should be able to differentiate the paraneoplastic syndromes from the benign disorders that mimic them. Patients with a suspected paraneoplastic disorder should undergo a complete panel of laboratory studies, in addition to imaging studies and endoscopy. Identification of paraneoplastic syndromes allow the clinician to make an early diagnosis and to provide adequate treatment of tumors, with a favorable oncologic outcome and improved life expectancy for the patient. These syndromes can follow the clinical course of the tumor and thus be useful for monitoring its evolution.     

MGMT基因与头颈肿瘤的相关研究

O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA methyltransfe-rase, MGMT)是DNA烷化剂损伤的主要修复酶,可保护基因烷化剂损伤导致的致突变、致癌作用。MGMT的表观遗传调控是影响其表达的主要机制。表达减少与肿瘤的发生发展的密切关系与其高表达增加肿瘤烷化剂化疗的耐药性成为一个互相矛盾的问题,此基因序列的单个核苷酸位点变异亦有可能与肿瘤发病风险相关。就MGMT基因在头颈肿瘤方面的研究做了综述。     

The dilemma of follow-up in head and neck cancer patients

The aims of tumor follow-up in head and neck cancer patients are (1) evaluation of therapeutic efficacy, (2) management of impairments, (3) detection of new tumor manifestations, and (4) psychosocial care. In general standardized 5-year-protocols are used for all such patients. However, it is questionable whether a rigid follow-up schedule is optimal for a very heterogeneous tumor population. Therefore 603 patients with sqamous cell carcinoma of the oral cavity, pharynx or larynx, or with cervical metastasis from an unknown primary site (CUP syndrome), who had been diagnosed and treated curatively by an operation with or without radiotherapy (n = 523) or just by radio(chemo)therapy (n = 80) between 1985 and 1994, and who had been followed-up regularly according to a standardized plan, were worked-up retrospectively. Data were evaluated for the manifestation and prognosis of curable new tumor manifestations as well as for tumor-specific factors likely to select groups which should be followed more or less intensively. Within a 5-year follow-up period new tumor growth was detected in 152/603 (25%) patients: 79 local and 31 regional recurrences, 18 systemic metastases and 24 second primary cancers. Where follow-up was extended beyond the 5th year, 168/603 (28%) patients presented a new tumor manifestation. One hundred and sixteen of the 152 (28%) patients had another operation with or without radiotherapy or had radio(chemo)therapy alone. So far 18/116 (14%) patients have survived their new tumor manifestation for more than 5 years and 30/116 for more than 2 years. Tumor-specific data on the initial tumors (T stage, N stage, site) did not indicate the risk of a new tumor manifestation, but 87% of patients who survived their new tumor manifestation for more than 2 years initially had T1 or T2 tumors and only 30% initially had N+ necks. Occurrence of distant metastasis or a second primary outside the head and neck region limited survival to ≤ 2 years after detection. In terms of survival, follow-up efforts should therefore concentrate on detection of locoregional recurrence, particularly if an option for further curative local therapy exists. The limited success of detection of new tumor manifestations in terms of survival does not justify a reduction in tumor-follow-up examinations, since the benefit of the other efforts cannot be determined from survival figures. Received: 29 January 2001 / Accepted: 8 February 2001     

Clinical significance of elevated osteopontin levels in head and neck cancer patients

OBJECTIVES: Osteopontin (OPN) is associated with several human malignancies, but the role of OPN in head and neck cancer (HNC) remains unclear. We investigated the clinicopathologic relevance of serum OPN levels in HNC patients. METHODS: Serum OPN levels in HNC patients were determined by quantitative sandwich enzyme immunoassay (EIA). OPN levels and their correlation with clinical features were examined. In addition, serum squamous cell carcinoma (SCC) antigen was examined simultaneously. RESULTS: The mean OPN level was significantly higher in HNC patients (99.5 ng/ml) than in control subjects (55.3 ng/ml). OPN levels were significantly higher in patients with advanced stage HNC than in patients with early stage HNC. OPN levels did not correlate with SCC antigen levels. CONCLUSIONS: OPN may play a role in the pathogenesis of head and neck cancer (HNC), and serum OPN may be a potential biomarker of HNC.     

High incidence of laryngopharyngeal reflux in patients with head and neck cancer

OBJECTIVES: Laryngopharyngeal reflux may play a role in the etiology of squamous cell cancer of the head and neck and contribute to complications in head and neck cancer patients after surgery or during radiotherapy. STUDY DESIGN: Prospective study. METHODS: To investigate the incidence of laryngopharyngeal and gastroesophageal reflux in patients with head and neck cancer, ambulatory 24-hour double-probe pH monitoring was performed in 24 untreated patients with laryngeal or pharyngeal squamous cell carcinoma. In addition, 10 patients who had been irradiated in the head and neck area were analyzed for reflux to study the effect of radiotherapy on reflux. RESULTS: Only 4 of the 24 head and neck cancer patients (17%) had neither pathological laryngopharyngeal nor gastroesophageal reflux. Esophageal acid exposure was abnormal in five patients and acid exposure at the level of the upper esophageal sphincter was abnormal in four patients. Eleven patients had pathological reflux in both areas. Irradiated patients did not differ from the untreated patients considering the incidence of pathological laryngopharyngeal or gastroesophageal reflux. CONCLUSIONS: The data obtained in this study indicate that reflux is a common event in head and neck cancer patients.     

CD73 expression in lymph node metastases in patients with head and neck cancer

Introduction: CD73 is an enzyme crucial in the metabolism of immunosuppressive adenosine. In cancer, it has various functions including tumor growth and metastases. Squamous cell carcinoma of the head and neck has an overall poor prognosis, also due to early spread of metastatic cells.

Materials and methods: Tumor and lymph node specimens of 65 patients with HNSCC were subjected to immunohistochemical and H-score analysis of CD73 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following locations: oral cavity n:16, oropharynx n:28, hypopharynx n:11 and larynx n:10. H-score for CD73 expression in the primary lesion and metastatic lymph nodes was significantly higher in advanced compared to early stages with no significant differences among tumor locations. High CD73 expression was associated with reduced overall survival rates at a mean follow-up of 83.4 months (6–204 months).

Conclusions: CD73 expression in HNSCC correlated positively with tumor stage and was associated with poor prognosis. Therefore, CD73 expression in primary lesions and regional metastases appears to predict HNSCC patients at high risk of all tumor sites. Therapeutic approaches targeting CD73 might seem promising for this patient population.     

Multiple primary malignant tumours in patients with head and neck cancer: the implications for follow-up

The pattern of second primary cancer occurrence in 518 Scottish patients with head and neck cancer was determined by a retrospective study. The overall incidence of second cancers was 9% but the true incidence increased steadily in the years following initial diagnosis to reach a maximum of 21% at 11 years. After 4 years of follow-up patients were more likely to die from a second primary cancer than from the effects of the initial tumour. The Scottish cohort differed from previously reported, overseas, study groups in having a high incidence of second primary cancers in sites outside the upper aerodigestive tract. This potential demographic difference suggests a need for local audit prior to design and implementation of screening protocols for second primary cancers.     

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.     

Management of cervical lymph nodes in patients with head and neck cancer

Summary The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer. Unfortunately, clinical assessment of the neck is not very accurate, although newer imaging techniques such as CT, MRI and ultrasound-guided fine needle aspiration cytology can be used to improve upon the results of clinical palpation alone. While diagnostic techniques remain less than 100% accurate, the risk of occult disease in the neck will remain. If this occurrence is judged to be greater than 15–20%, elective treatment to the neck may then be justified. When the neck is treated surgically, histological information can be gained which has both prognostic and therapeutic implications. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of the neck and the results of such treatment are discussed.     

The nature of the head and neck cancer

Summary Squamous cell carcinoma of the head and neck is a disease predominantly of males and is due to a variety of known environmental irritants, notably cigarette smoke. Dietary, viral and immunological factors may also be relevant. Head and neck squamous cancers express epidermal growth factor receptors and some show weak levels of oestrogen receptor activity, but a reliable serum marker of tumour burden remains to be identified. The prognosis is found to be less favourable in females, in those with advanced T stage, in association with multiple node involvement, especially where extracapsular spread is present and where the T4/T8 ratio is elevated. Administration of heterologous blood during therapy may also have an adverse effect on prognosis. Interested clinicians must remember that most cases are preventable. Correspondence to: A.G.D. Maran     

Limited use of complementary and alternative medicine in Israeli head and neck cancer patients

HYPOTHESIS/OBJECTIVE: The use of complementary or alternative medicine (CAM) is growing among cancer patients. A Medline search failed to reveal any dedicated report of CAM use specifically in patients with head and neck cancer (HNC). STUDY DESIGN: Use of CAM was evaluated in a cohort of treated HNC patients. METHODS: Patients treated for HNC were asked if they had used CAM since their diagnosis. Demographic data and data pertaining to mode of CAM, duration of treatment and effects were obtained. RESULTS: One hundred forty-three patients (mean age 61 years) were included. Only nine patients (6.3%) reported using disease related CAM. This included acupuncture (4), Reiki (2), naturopathy (2), hypnosis (1), shiatsu (1), chiropractic treatment (1), homeopathy (1), and selenium (1). CONCLUSION: Contrary to the reported use, few of our HNC patients used CAM. Although this could be related to good caregiver-patient relationship, further studies in comparable populations are warranted to evaluate if this is a local or a pervading finding in head and neck cancer patients.