The role of chemotherapy in head and neck cancer

We studied the effect of cytoreductive chemotherapy in head and neck cancer and analyzed it in terms of efficacy, remission rates, and duration, as well effect on survival. Single-agent chemotherapy, which formerly was used as a palliative therapy in recurrent and metastatic disease, had little affect on survival. More recently, multi-agent chemotherapy trials have shown significantly higher response rates, but this success has not translated into an added survival benefit. These findings led to the introduction of multi-agent chemotherapy into the induction (neoadjuvant) clinical setting. In these clinical circumstances, better objective response rates were found, particularly in the previously untreated patient. Although this therapy has resulted in better control of local disease, the impact on survival is not yet clear. Adjuvant chemotherapy is most useful in patients who have a high risk of relapse. Therapy appears to decrease its incidence, particularly at distant sites. Finally, chemoradiation trials have shown that this treatment provides a survival advantage, but at the cost of a significant increase in toxicity.     

Radiologic diagnosis and staging of head and neck squamous cell carcinoma

The predominant extracranial head and neck cancer in adults is squamous cell carcinoma. The purpose of this article is to discuss the radiographic evaluation of these patients with computed tomography (CT) or magnetic resonance (MR) imaging prior to therapeutic intervention. Specific focus is given to the efficacy of CT and MR imaging, as an adjunct to clinical staging, for evaluation of the primary tumor, and metastatic adenopathy. MR imaging, because of its improved soft tissue contrast and multiplanar capability, is probably superior to CT for evaluation of the primary tumor in patients with squamous cell carcinoma. CT, however, remains the gold standard for identifying metastatic adenopathy and in most institutions remains the study of choice for evaluating this patient population.     

Immunotherapy of head and neck cancer

Understanding the mechanisms responsible for photodamage to the skin is most important for dermatology. 3-D cultures have been used as tools to mimic the in vivo situation for several years. We irradiated such a system containing human dermal fibroblasts cultured in collagen gels, a well-known model considered to be a dermal equivalent, which reproduces the interaction between cells and the surrounding extracellular matrix. The effects of solar irradiation (315-800 nm) on the steady-state levels of the mRNAs of extracellular matrix components (type I and III collagens) and their degrading enzymes (interstitial collagenase, MMP-1 and stromelysin 1, MMP-3) were measured. Exposure to low levels of solar radiation (0-10 J cm-2 in the UVA, i.e. suberythemal UVA doses) caused a transient decrease in type I procollagen mRNA, an increase in MMP-mRNA, and no change in type III procollagen mRNA steady-state levels. These results describe the early changes in the connective tissue of the skin following exposure to low-level solar stimulation, and may help explain the long-term changes in photodamaged skin.     

Chemoprevention of head and neck cancer

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.     

Moderate-dose methotrexate in head and neck cancer

200 mg/m2 methotrexate given intravenously in a running drip for 6 h has been used as an initial adjuvant therapy in 38 patients with advanced head and neck cancer. The response rate is as high as 80%, with 21% achieving complete remission. Histologically, specimens were tumor free in 3 patients. Toxicity in 38 patients included leukopenia (4), mucositis (6) and diarrhea (1). This particular dose of methotrexate appears to be safe and usually does not need leucovorin rescue. Also, when given as initial treatment, it is effective in reduction of tumor bulk. A prolonged randomized trial is essential to determine its role in improving long-term survival.     

Sexuality in head and neck cancer patients

We describe a patient with Hirschsprung disease and autism. High-resolution karyotyping indicated that the patient has an interstitial deletion of 20p11.22-p11.23. Microsatellite analysis showed a deletion involving a 5-6 cM region from the maternally derived chromosome 20. The deleted region is proximal to, and does not overlap, the recently characterized Alagille syndrome region. This region of 20p has not yet been implicated in Hirschsprung disease or autism. However, this region contains several genes that could plausibly contribute to any phenotype that includes abnormal neural development.     

FDG PET in head and neck cancer

In our extensive experience with FDG PET imaging in head and neck cancer, we have found the technique to be of high accuracy but of limited usefulness. This seeming paradox arises from several causes. Competing techniques such as CT, MR imaging, and even clinical examination already have good accuracy. In addition, high-resolution studies such as CT and MR imaging provide information required for treatment planning that is unavailable from FDG PET images. The high cost of FDG PET militates against its use in this setting, in which only a small marginal gain can be expected. In the special problem areas in which FDG PET might be expected to offer unique advantages, such as screening for second primary lesions, searching for unknown primary lesions, or differentiating benign salivary rumors from malignant lesions, the results of FDG PET have been disappointedly poor. Of these special problem areas, only the question of accuracy in finding occult primary lesions appears unresolved and in need of further study. The single application in which FDG PET appears to be advantageous is the posttherapy setting. In this setting, the technique is definitely superior to alternative methods of determining tumor recurrence and differentiating posttherapy sequelae such as radiation necrosis from tumor recurrence. We believe that considerable opportunity remains for further research on the use of FDG PET in head and neck cancer. Other agents such as 11C-methionine for example, might improve the diagnostic accuracy of FDG PET in some of the problem areas that we have identified, such as the early postirradiation period. We currently have such a study under way. Also, because FDG PET offers a unique way to measure tumor metabolism, further investigation of the use of FDG PET tracers to evaluate various biologic parameters such as proliferation rates or tumor hypoxia are needed. Such studies could provide a noninvasive technique to identify which fractionation schemes or combinations of therapy might be useful for individual patients. A final caveat is in order. Although our findings of the usefulness (and lack thereof) of FDG PET in head and neck cancer may be disappointing to many, these results should not be generalized to other applications of FDG PET in oncology. Each tumor type and setting presents its own specific problems, and in some instances FDG PET offers unique advantages over other imaging techniques. A good example is the setting of primary lung cancer, in which FDG PET appears clearly superior to all other methods of pretherapy screening [19-20].     

Suicide in head and neck cancer patients

PURPOSE: It has been well documented that patients with a diagnosis of cancer are at an increased risk of committing suicide. However, there is a paucity of literature on the risk of suicide in the head and neck cancer patient. The purpose of this investigation was to determine the incidence of suicide and expressed suicidal intent in a series of such cancer patients. PATIENTS AND METHODS: A retrospective chart review of 241 patients who were diagnosed with head and neck cancer at the University of Maryland Oral and Maxillofacial Surgery Oncology Division was done. RESULTS: Three patients were identified who committed suicide, 1.2% of the series. Two patients expressed suicidal intent, and four patients refused all treatment and counseling, preferring to die of their disease. CONCLUSIONS: Head and neck cancer patients have many of the same risk factors for suicide as patients with other forms of cancer. To reduce this risk, it is essential that the surgeon maintain good rapport with the patient, because this serves as a foundation for all other aspects of their therapy. In addition, these patients need to be fully evaluated for depression, hopelessness, pain, and other factors important in raising the possibility of suicide, and appropriate, aggressive management must be provided.     

Skin cancer of the head and neck

The incidence of skin cancers is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious skin lesion may first present to their primary care physician for evaluation. Therefore, it is important for the primary care physician to be able to distinguish between benign and malignant pigmented lesions, to know how to evaluate such a patient, and to appreciate the importance of appropriate interdisciplinary management of these patients.     

Intraoral reconstruction in head and neck cancer surgery

The effect of prostaglandins (PGs) on the hepatic biotransformation of hexobarbital (Hechi) and p-chloro-N-methylaniline (PCMA) was determined in male rats. PCMA metabolism in slices was decreased by all PGs (PGA1, PGB1, PGE1, PGE2, PGF1alpha, PGF2alpha), ranging in concentration from 1 mu M to 1 mM. PGA1, at 1 mM, produced the greatest degree of inhibition, 39%. PG addition to microsomes, however, failed to alter PCMA metabolism. In contrast to PCMA biotransformation, Hechi metabolism was increased by all PGs in slices but not in liver subfractions. PGs of the E and F series were the most potent, producing a two-fold increase in Hechi metabolism at 1 mM after a 20 min preincubation. The increased effect was observed as early as 10 min and lasted for 4 hr. The relationship of PG metabolism and binding to cytochrome P-450 is presented as a possible mechanism to account for the opposite effects on Hechi and PCMA, type I and II substrates respectively, metabolism.     

Cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors and their role in head and neck cancer

Electrical kettles (el-kettles) were virtually unknown in Danish households in the mid-1980s, but have since become more common. In 1996, (65 per cent of all Danish households had an el-kettle. As the number of el-kettles have increased, so have the number of scalds caused by water from toppled el-kettles. The first patient with an el-kettle scald was admitted to the Burns Centre at Hvidovre hospital in 1988. From 1988 to 1993 29 patients were admitted with this type of scald; 15 patients in 1993 alone. All the patients were toddlers 5-30 months of age. When el-kettle scalds were compared to scalds caused by other mechanisms in children under 5 years of age, it was found that the former occurred to younger children than the latter (60 per cent of el-kettle scalded children were less than 1 year of age compared to 28 per cent scalded by other means), the scalds were more extensive (median of TBSA were 13 per cent and 6 per cent, respectively), and the scalds were deeper (53 per cent and 24 per cent, respectively, needed skin-grafting). In 1993 campaigns were started to inform parents that the cord of the el-kettle should be short and not hang over the edge of the table. In the following years a considerable decrease in the number of el-kettle scalds was found. When the number of expected el-kettle scalds was estimated from the number of Danish households having an el-kettle, it was found that more than half the expected number of el-kettle scalds were avoided.     

Facial disfigurement in patients with head and neck cancer: The role of social self-efficacy.

This study investigated the moderating role of social self-efficacy (i.e., the belief that one is capable of exercising control over the reactions and openness of other people) with respect to the link between facial disfigurement and psychological and n = 76) as well as their physicians. In line with the hypotheses, the results revealed that the degree of facial disfigurement, as judged by patients as well as their physicians, was positively related to psychological distress and distress in reaction to unpleasant behavior of others, but only when patients did not feel self-efficacious in social encounters. Furthermore, social self-efficacy mitigated the positive link between facial disfigurement as judged by patients and social isolation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The nature of the head and neck cancer

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.     

Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors

OBJECTIVE: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis. DESIGN: A retrospective study of observational data. SETTING: Regional neurosurgical unit and intensive care unit. PATIENTS: Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2). MEASUREMENTS AND MAIN RESULTS: Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern p = .01 1). CONCLUSIONS: Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase.     

Ongoing trials in patients with head and neck cancer

Treatment of squamous cell carcinoma of the head and neck has recently undergone several important changes. New approaches to treating these tumours are now being evaluated. An overview of the surgical, radiotherapeutic and chemotherapeutic therapies or multimodality approaches currently under study are described. In addition, the design of ongoing chemoprevention trials is reported.     

Delayed hypersensitivity skin test in head and neck cancer

A brief introduction is given stressing the importance of host reactions against tumour specific antigens. Two groups of patients are presented. Positive tests are associated with a better prognosis in both groups. Energy is commonly associated with widespread disease, but other factors appear to be concerned as well. Immune competence is impaired soon after surgery, but as time progresses this appears to recover. Tumour bulk appears to be the biggest barrier to the immune mechanism and it would appear that the role of immunotherapy in the future will be to supplement more conventional methods of treatment, especially surgery.     

Ionized serum calcium levels following combined treatment for cancer of the head and neck

Thyroid function may be reduced after treatment of cancer of the head and neck, and hypothyroidism is much more common after combination therapy. Whether hypoparathyroidism and subsequent hypocalcemia also occur after such treatment is unknown. Few related studies have been published in which changes in total serum calcium have been studied after cancer treatment with radioactive iodine or external radiation. Twenty-two disease-free head and neck cancer patients were studied, 1 to 3 years after multimodal treatment, to determine if changes in serum ionized calcium levels or thyroid function were present. Our results suggest that parathyroid function, as represented by ionized calcium levels remains normal after multimodality (surgery, radiation and/or chemotherapy) combined treatment.     

Current options in management of head and neck cancer patients

Head and neck cancer, particularly squamous cell carcinoma (SCC) of the upper aerodigestive tract, poses difficult diagnostic and therapeutic challenges to the clinician. A methodical approach, including complete visualization of mucosal surfaces, appropriate imaging, and tissue diagnosis whenever possible, gives patients the best opportunity for early intervention. A treatment program of surgery, radiation, or chemotherapy is best developed by a devoted head and neck oncologic team, involving surgeons, radiation and medical oncologists, and rehabilitative specialists with significant experience in the care of head and neck oncologic patients. Despite new advancements in the treatment of patients with advanced stage SCC of the head and neck, little progress has been made in overall survival. Several new avenues of investigation are currently being explored, one of which may ultimately provide the answer for this devastating disease.     

Symptom management for incurable head and neck cancer

The overall cure rate for cancer of the head and neck is about 50%. For those patients who will die of their disease, active palliative care is needed. This article seeks to present a practical approach to managing the symptoms, especially pain, suffered by patients with incurable malignancy. (See related article, Using Opioids to Control Suffering: A Painstaking Approach, on page 20 of the February, 1997 WMJ.) While the focus is on head and neck cancer, the principles and much of the information contained herein is applicable to patients dying from other types of malignant disease.