Samuel R. Fisher

Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer

BACKGROUND Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

Cutaneous malignant melanoma of the head and neck

A computer‐aided analysis of 5,109 patients with malignant melanoma was performed. Patient population characteristics according to body site (head and neck, extremity, and trunk) were determined for the following parameters: sex, histologic type of melanoma, Clarks level, Breslow thickness, age, clinical status of regional nodes, presence or absence of ulceration, and recurrence. Head and neck melanomas accounted for 17% of the total population (N=877). A detailed analysis of general population characteristics according to subsites within the head and neck region (ear, face, neck, nose, and scalp) was performed. Survival characteristics were determined for head and neck patients according to lymph node surgery, histologic type of tumor, and tumor thickness. The effect on survival of lymph node dissection (elective for stage I disease and therapeutic for stage II disease) was analyzed by univariate and multivariate methods. Elective lymph node dissection (ELND) was performed on 77 patients and 39 patients underwent therapeutic nodal dissection (TLND). Overall, survival was significantly improved following ELND as compared to TLND; however, multivariate analysis indicated the improved survival was related to variations of age within the population rather than the beneficial effect of lymph node surgery. Elective lymph node dissection did significantly reduce the incidence of recurrence for head and neck patients (p=0.002). Since recurrence was demonstrated to be directly related to survival, the trend toward improved survival following ELND after 5 years was felt to be important. There was no difference in survival according to the histologic type of melanoma.

Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: Two case studies

Angiosarcoma of the face is a vascular tumor with poor local control and short median survival despite standard treatment. Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), which can inhibit tumor growth. It is synergistic with radiotherapy in gastrointestinal malignancies. Given the vascular nature of angiosarcoma and the need for better treatment of this disease, we investigated the concurrent use of bevacizumab with preoperative radiotherapy for head and neck angiosarcoma.

Otolaryngologic management of patients with subdural empyema

From 1979 to 1988,17 patients presented to Duke University Medical Center for treatment of subdural empyema. Empyemas were caused by sinusitis in 53% of the patients and by otitis media in 12%. None of those with otologic causes required mastoid drainage, while all patients with sinus infections required sinus drainage. External frontoethmoidectomies were associated with a lower incidence of fronto‐ethmoid re‐exploration (P = 0.048), and antrosto‐mies with a lower incidence of maxillary re‐exploration (P = 0.111), than were more limited drainage procedures. Sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re‐exploration (P = 0.167), neurosurgical re‐exploration (P = 0.048), and length of hospitalization (P = 0.020).

5-Fluorouracil, cyclophosphamide, and vincristine for adenoid cystic carcinoma of the head and neck

Twenty‐one patients with adenoid cystic carcinoma of the head and neck were treated with intravenous boluses of cyclophosphamide and vincristine and 5‐day continuous intravenous infusions of 5‐fluorouracil (CVF) every 4 weeks. Eight patients received CVF as palliation for recurrent or metastatic disease. A sustained complete response (107+ months) was observed in one patient; one partial response and one mixed response each also were observed. In four patients disease stabilized, and in one disease progressed. Thirteen patients received six courses of CVF in the adjuvant setting after surgery and radiation for either primary or locoregional recurrent disease. Recurrences developed in two of seven patients with primary disease and three of six patients with recurrent disease with a median follow‐up 45 months (range, 20–108+). Recurrence rate and time interval to recurrence were comparable to those of well‐matched historical controls. Distant metastases have not developed in patients treated with CVF in the adjuvant setting, whereas distant metastases had developed in historical controls within comparable periods of follow‐up. Serious toxicities were not encountered in any patient. The authors conclude that CVF is a well‐tolerated combination chemotherapy program with activity in adenoid cystic carcinoma of the head and neck. This regimen, however, has not had a major impact in the adjuvant setting in preventing recurrent disease. Cancer 59:887‐890, 1987.

The effect of head and neck radiation therapy on voice quality

Twenty‐five patients with squamous cell carcinoma of the head and neck who received radiation therapy as their only form of treatment underwent a computer‐assisted voice analysis before, and 6 months following treatment. Those with early laryngeal tumors had a significant improvement in intelligibility (P = .07), percent of sound voiced (P = .04), and sound perturbation. Those with nonlaryngeal tumors had no change in any measured parameters. Head and neck radiation therapy can significantly improve the voice quality of patients with laryngeal tumors, while having a minimal effect on the voice quality of those with nonlaryngeal tumors.

Penile Metastasis Secondary to Supraglottic Squamous Cell Carcinoma: Review of the Literature

We report an unusual supraglottic carcinoma metastasis to the penis. Review of the literature revealed more than 300 cases of metastatic lesions to the penis, excluding primary neoplasms from skin, urethra and blood. Of these metastatic neoplasms 16 originated above the diaphragm, only 4 of which were from the head and neck region. The most common neoplastic metastases to the penis in order of frequency were from the bladder, prostate, rectum and rectosigmoid areas, and kidney in 32, 30, 13 and 8% of the cases, respectively. The incidence of other primary tumor sites that metastasize to the penis is extremely rare.

Elective, therapeutic, and delayed lymph node dissection for malignant melanoma of the head and neck: Analysis of 1444 patients from 1970 to 1998

Objective The purpose of this article is to evaluate the effects on survival, disease‐free interval, and recurrence patterns for patients undergoing elective, therapeutic, and delayed lymph node dissection for malignant melanoma of the head and neck.

Melanoma of the ear: treatment and survival probabilities based on 199 patients.

Background:In 2005, it is now estimated that one in 62 Americans have a lifetime risk of developing invasive melanoma. Melanoma of the ear accounts for 1% of all cases of melanoma and 14.5% of all head and neck melanomas. With this increase in incidence, plastic surgeons will likely have to treat and manage more of these patients in the future. Methods:A retrospective chart review was performed on 199 patients diagnosed with primary melanoma of the ear. Specimens were reviewed by same center dermatopathologists (Duke University Medical Center, Durham, NC) for standardization of histologic criteria in all but 10 patients. Surgical treatment and outcomes were reviewed and survival rates based on thickness and stage were calculated. Metastases information, anatomic location on the ear, and histologic subtype were recorded and analyzed. Results:The median length of follow up was 3.3 years with a range of 0.4 to 24.9 years. Eighty-six patients were known to be dead at the last known follow-up date. The median survival time among these patients was 7.9 years. The most common histologic classification of the lesions were superficial spreading type (45.2%) and were most likely to be localized to the anterior helix (49.3%). One hundred sixty-one of 199 (80.9%) patients underwent wide local excision with local recurrence rate of 10.6%. Overall, 43.2% of patients developed a local recurrence or metastatic spread. Ulceration, thickness, and stage all negatively affected survival. Conclusions:This is the largest review of primary ear melanoma cases reported to date. Survival probabilities at 2, 5, and 10 years for melanoma of the ear based on thickness and stage are presented. Ulceration adversely affected survival probability (P < 0.003). Lesion excision with confirmed negative margins on permanent section pathology should be the goal of initial surgical therapy, and there is no apparent role for elective lymph node dissection in treatment of melanoma of the ear.

A phase I/II trial of twice daily irradiation and concurrent chemotherapy for locally advanced squamous cell carcinoma of the head and neck

PURPOSE This study was designed to test the toxicity and efficacy of a regimen of twice daily irradiation and concurrent multiagent chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS This was a prospective Phase I/II trial. Patients received 125 cGy b.i.d. to 7000 cGy with a 6 hr interfraction interval. Chemotherapy was given during weeks 1 and 6 of irradiation and consisted of a 5 day infusion of 5-fluorouracil at 600 mg/M2/day and 5 daily injections of cisplatin at 12 mg/M2/day. Two additional cycles of chemotherapy were given after the completion of radiotherapy. RESULTS Forty-six patients were evaluable: 28 had technically unresectable disease and 18 had resectable tumors. All had Stage III or IV disease: 84% had T3 or T4 primaries while 53% had > or = N2 neck disease. The primary acute toxicity, confluent mucositis, was seen in 74% of patients. Late side effects occurred in four patients. Median follow-up is 36 months (range 25-44 months). Kaplan-Meier estimates of 2-year disease-free survival and overall survival are 65% and 73%, respectively, while 2-year local regional control and distant disease-free survival are 72% and 88%, respectively. Multivariate analysis revealed that resectability and receiving > 2 cycles of chemotherapy significantly influenced local regional control while age < 60 significantly influenced disease-free survival. CONCLUSION This form of treatment can be delivered safely. The encouraging results have led to the initiation of a Phase III trial comparing this regimen with b.i.d. radiation alone.