Complicating mucosal reactions in patients receiving radiation therapy for head and neck cancer

Radiation mucositis is characterized by erythema, pseudomembranes, and ulceration of mucosa in the irradiated field. We present two cases of oral mucosal changes in patients treated with radiotherapy in the head and neck region, which included mucosal erythema and ulceration outside of the radiated fields. One case was confirmed as herpes virus infection, and the other was diagnosed as Sweet's syndrome. When mucositis extends beyond the radiation fields, the clinician should consider other causes of mucosal inflammation and erythema in order to begin appropriate management.     

Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study

PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.     

High-dose rate intracavitary radiation therapy for advanced head and neck tumors

Fifty-seven treatments were performed on 27 head and neck pateints with recurrent or residual tumors on a high dose rate, remote controlled afterloading unit: There were 16 cases of maxillary sinus tumors, 6 epipharynx, 3 alveolar ridge, 1 hard palate and 1 floor of mouth. All patients have been followed up more than 2 years except one. Five patients are alive without local recurrence for more than 2 years. In 13 patients local tumors disappeared once and normal mucosa covered the tumor sites. Two patients died from local bleeding. In six patients this method failed to destroy tumors. Our prupose was palliative local control: therefore, in two-thirds of cases treated we were successful with this easy method of nonfractionated acute intracavitary radiation. This result is favorable, considering that all cases treated here were failures following full dose external radiation, although the treatment had to be repeated more than twice in 15 cases. Relief of symptoms is excellent when this therapy is used.     

Accelerated fractionation (AF) in head and neck cancers

A carpal boss is frequently caused by a bony anomaly of the quadrangular joint of the carpus. We present the case of a patient with a carpal boss caused by an accessory capitate.     

The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer

PURPOSE: The purpose of this study was to develop and validate an instrument for clinical trials to measure radiation-related acute morbidity and quality of life from the perspective of patients with head and neck cancer (HNC) treated with radiotherapy. METHODS: The Head and Neck Radiotherapy Questionnaire (HNRQ) was developed by a panel of health care workers and patients, was pretested in a pilot study of HNC patients, and was validated in a randomized double-blind trial of concomitant fluorouracil (FUra) infusional therapy (1.2 g/m2 per 24 hours) or saline placebo administered for 72 hours in the first and third weeks of a 6 1/2-week course of radiation therapy. The HNRQ was validated against existing toxicity and performance status indices, all of which were measured weekly for the 6 1/2 weeks of treatment and for 4 weeks posttreatment. RESULTS: There were three a priori constructs: (1) that the HNRQ scores would conform to a shallow U-shaped pattern to reflect declining quality of life (increasing morbidity) during radiation and recovery posttreatment; (2) that the HNRQ would correlate with existing toxicity indices (World Health Organization [WHO] stomatitis, Byfield stomatitis, WHO skin toxicity, Eastern Cooperative Oncology Group [ECOG] and Karnofsky performance status); and (3) that the HNRQ would discriminate between FUra and placebo groups. The HNRQ and its domain scores all showed a change from baseline reflecting increased morbidity during radiation (analysis of variance [ANOVA], P < .00001). The HNRQ correlated well with all other indices (r > or = .60), and domain scores correlated best with other indices that assess the same symptom complex (eg, HNRQ skin domain and WHO skin toxicity index, r = .77). There was a significant difference in HNRQ scores between the FUra and placebo groups during radiation (ANOVA, P = .0007), and all HNRQ domains also discriminated between the treatment groups. CONCLUSION: The HNRQ is a valid measure of acute morbidity due to radiation therapy in patients with locally advanced HNC, and may be useful as an outcome measure for future clinical trials of radiation treatment strategies.     

Nutritional and zinc status of head and neck cancer patients: an interpretive review

Adipose tissue is considered as the body's largest storage organ for energy in the form of triglycerides, which are mobilised through the lipolysis process to provide fuel to other organs and to deliver substrates to liver for gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids is intensively regulated by hormones and agents. In man, the major hormones are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Physiological factors such as dieting, physical exercise and ageing also regulate lipolysis. The lipolytic process is modified in pathological conditions, e.g. obesity (both upper and lower obesity), diabetes (non- and insulin-dependent diabetes mellitus), and dyslipidaemia (in particular, familial combined hyperlipidaemia). The regulation of lipolysis is complex because of the heterogeneity of fat depots (visceral versus subcutaneous), which may contribute to the well-known gender differences in accumulation of fat. Since visceral fat depot is directly drained into the liver and has a high turnover of visceral triglycerides, "portal" free fatty acids seem to be an important pathophysiological factor in common complications of obesity (in particular, metabolic syndrome). New advances in genetic studies indicate that polymorphisms in several genes encoding for proteins that regulate the lipolysis process are important for the development of obesity and its complications.     

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study

PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.     

Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy

Although it is established that small and medium sized arteries undergo extensive radiation damage, the effect on large vessels such as the carotid arteries is less well understood. We sought to determine if an increased severity of carotid artery stenosis is present in patients who have undergone radiotherapy for head and neck tumours. 45 patients aged 43-90 years (average 67) with head and neck malignancies treated with radiotherapy underwent colour Doppler ultrasonographic scanning of the carotid arteries. These patients were compared with a population of asymptomatic historical controls. 60% of patients demonstrated stenosis ranging from 21 to 86%. 38% of patients demonstrated a stenosis greater than or equal to 50%. Carotid artery stenosis appears to be increased in patients who have previously undergone treatment with radiotherapy to the head and neck regions compared with controls (p < 0.001). These findings suggest that radiation has an adverse effect on large vessels. Colour Doppler follow-up may be indicated for patients receiving head and neck radiation therapy.     

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.     

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.     

Combined radiochemotherapy for organ preservation in head and neck cancer: review of literature and personal experience

Combined radiochemotherapy is the most common method aimed at improving the rate of clinical response in advanced head and neck cancer. Complete clinical remission may correspond to a significant percentage in organ and/or function preservation. In 1992 a protocol of concomitant radiochemotherapy with continuous infusion of carboplatin for 14 consecutive days at the daily dose of 30 mg/m2 and concomitant radiotherapy with conventional fractionation (1.8 Gy to a total 65-70Gy) was started. Over a 3-year period, 56 patients with advanced head and neck cancer, were treated. In view of organ preservation, 26 patients of this series, though with considerable extent of the disease at diagnosis, were considered candidates for radical surgery: oral cavity 9 patients; oropharynx 9 patients; larynx/hypopharynx 8 patients. A single patient was stage I (hypopharynx); most patients were stage III (7) and IV (17 = 65%); T4 20%, N3 23%. 17/20 patients (70%) showed complete clinical response, 6 partial clinical response with a single non responder (overall response 95%). A patient underwent total glossectomy followed by local recurrence and another patient underwent pharyngolaryngectomy also followed by recurrence. After a mean follow-up from 22 to 60 months, 9 patients were still free of disease (37.5%). Median duration of complete response was 25.6 months. Overall median survival was 26.7 months: 38 months in responders. 2-year survival of patients with complete response was 59%. As for organ preservation, at present 6 over 18 patients (33%) with tumor of the oral cavity or oropharynx and 3 patients with tumors of larynx/hypopharynx have preserved organ and function. As for complete responders, 54.5% of those with tumors of oral cavity or oropharynx and 50% of those with tumors of larynx/hypopharynx, have preserved anatomy and function after at least 2-year follow-up. To-date, in follow-up controls relevant late toxicity has not been observed, showing that to the positive anatomical result corresponds the functional preservation of single structures.     

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.     

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review

BACKGROUND: The limited efficacy of current approaches to the treatment of patients with hepatic cancer, including external beam radiation therapy and cytotoxic chemotherapy, has reawakened interest in the use of internal radiation therapy. METHODS: The authors reviewed series of patients with liver metastases or hepatocellular carcinoma (HCC) treated with 1) interstitial irradiation and direct intratumoral injection of 90Y microspheres, 2) intraarterial infusion of (131)I-Lipiodol, 3) intraarterial infusion of 90Y microspheres, or 4) parenteral administration of radiolabeled monoclonal antibodies. RESULTS: High dose rate interstitial irradiation with afterloading of (192)Ir resulted in local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients. Direct intratumoral injection of 90Y microspheres reduced the size of 90.6% of tumors and completely destroyed them in 8 patients. Treatment with arterial (131)I-Lipiodol resulted in a 17-92% response rate as well as a case of complete remission of unresectable HCC. It was found to be most effective against small tumors. No response was observed with liver metastases from colorectal carcinoma. Partial response was commonly achieved when patients with unresectable liver metastases or HCC were treated with intraarterial 9OY microspheres. Among four patients whose HCC became resectable following treatment with 90Y microspheres, two cases of complete remission were documented. In a prospective randomized trial, (131)I-antiferritin combined with chemotherapy was no more effective than chemotherapy alone. CONCLUSIONS: The different approaches to internal radiation therapy that are reviewed in this article represent several ways in which radiation can be selectively targeted to hepatic tumors without undue radiation to the nontumorous liver. However, the efficacy of each of these therapies still needs to be evaluated in randomized controlled trials.     

Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis

PURPOSE: Our purpose was to determine the sensitivity, specificity, and receiver operator characteristic (ROC) curve of a fast screening MR protocol in children and adolescents with suspected intracranial tumors. METHODS: One hundred forty-one patients (mean age, 9.7 years; range, 2 months to 23.5 years) with suspected brain tumor were entered in a case-control study. Eighty-seven patients had intracranial tumors (31 suprasellar/hypothalamic, 27 supratentorial, 26 infratentorial, and three pineal) and 54 patients in the control group had other disorders. Two neuroradiologists reviewed blindly a detailed three-sequence conventional protocol (acquisition time, 8 minutes 27 seconds) and a two-sequence fast screening MR protocol (acquisition time, 4 minutes 44 seconds). RESULTS: Sensitivity and specificity of the fast screening protocol for intracranial tumors was 100% and 92.6%, respectively. The areas under the ROC curves were 0.966 for the fast screening and 0.980 for the conventional MR protocol. No diagnostic performance difference was found between the ROC curves using the Az index. A kappa statistic of .93 for both examinations indicated excellent interobserver agreement. Additional MR sequences and other neuroimaging studies were not deemed necessary to exclude the presence of an intracranial tumor. CONCLUSION: A fast dual-plane brain MR protocol may be adequate to screen children and adolescents thought to have an intracranial tumor. The less than 5 minute acquisition time allows a complete examination (including preparation) to be performed in 10 to 15 minutes. Future studies are recommended before this time-efficient neuroimaging examination is incorporated into clinical practice.