Barry L. Wenig

Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.

Objectives: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease.

Salvage treatment for recurrent squamous cell carcinoma of the oral cavity.

Squamous cell carcinoma (SCCA) of the oral cavity recurs with a frequency of 25%–48%, a fact that usually portends a poor prognosis. Recent studies have reported salvage cure rates as high as 67%. Investigators have also claimed that restaging recurrent tumors provides useful prognostic information, although this has not been demonstrated with tumors of the oral cavity. The purposes of this study were: (1) to report the patterns of recurrent SCCA of the oral cavity; (2) to examine the benefit of restaging oral cavity tumors, and (3) to compare different treatment modalities in the management of recurrent SCCA of the oral cavity.

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer

The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck.

Inflammation in the Uvula Mucosa of Patients With Obstructive Sleep Apnea

This study was conducted to determine whether inflammation is present in the uvula mucosa of patients with obstructive sleep apnea (OSA). Uvulas were obtained by uvulopalatopharyngoplasty in 21 patients with moderate OSA (mean apnea/hypopnea index and standard error of the mean: 32±4) and by autopsy in 5 individuals not known to have OSA.

Induction chemotherapy followed by concomitant chemoradiotherapy for advanced head and neck cancer: impact on the natural history of the disease.

PURPOSE To determine survival rates and the pattern of failure in head and neck cancer patients treated with induction chemotherapy, limited surgery and concomitant chemoradiotherapy. PATIENTS AND METHODS Three cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optional surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concurrent radiation for 5 days (FHX) for a total radiation dose of 65 to 75 Gy. Surgical resection was performed with the intent to spare organ function. RESULTS Seventy-one patients were treated at three institutions. Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achieved a clinical complete response (CR) to PFL-IFN. Local therapy consisted of surgery in 37 and/or FHX in 55 patients. With a median follow-up duration of 37 months, there have been 20 recurrences (15 local, four distant, and one both local and distant), and 29 deaths, 15 in patients with disease progression and 14 not directly related to the primary tumor. Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60% (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mucositis (54%) and myelosuppression (60%). Five patients died of toxicity. During FHX, 70% of patients had grade 3 or 4 mucositis. CONCLUSION PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant control and overall survival rates. Second malignancies and intercurrent medical disease emerge as major risks to long-term survival. In view of the high toxicity and long treatment duration, further modifications of this approach are required.

Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival.

PURPOSE To determine tumor response rate, patterns of failure, toxicity, and survival in advanced squamous head and neck cancer after a combined treatment program that consists of induction chemotherapy, organ-sparing surgery, and concurrent chemoradiation. Long-term outcome data are presented. PATIENTS AND METHODS Between July 1991 and March 1993, 93 patients received three cycles of induction chemotherapy that consisted of cisplatin, fluorouracil (5-FU), l-leucovorin, and alpha-interferon2b (PFLl-alpha) followed by optional limited surgery and six to eight cycles of 5-FU, hydroxyurea, and concurrent radiation (FHX) to a total radiation dose of 65 to 75 Gy. RESULTS Ninety-three patients were entered onto this study and 97% had stage IV disease, with 66 patients who were N2 or N3. Sixty-one patients (66%) achieved a clinical complete remission (CR) after induction therapy. Thirty-four patients underwent surgery. Seventy-nine patients proceeded to FHX. With a median follow-up time of 43 months for surviving patients, 20 patients have had disease progression (13 local, two distant, five both), and there have been 35 deaths (18 from disease, six treatment-related, two from a second primary, and nine for other medical reasons). At 5 years, progression-free survival is 68%, and overall survival is 62%. Surgery was organ-preserving, as only a single laryngectomy and no glossectomies were performed in primary management. Acute toxicity related to PFLl-alpha consisted of severe or life-threatening mucositis in 57% and leucopenia in 65% of patients. During FHX, 81% of patients had grade 3 or 4 mucositis. CONCLUSION PFLl-alpha is a highly active regimen that induced clinical CR in two thirds of patients. When followed by limited surgery and FHX, resultant local and distant disease control, organ preservation, and overall 5-year survival are very promising in high-risk stage IV patients. Based on these local control and survival data, further evaluation of this treatment sequence, induction chemotherapy followed by concurrent chemoradiation, is warranted. Identification of similarly active but less toxic regimens is a high priority.

Complications of percutaneous endoscopic gastrostomy in head and neck cancer patients

Percutaneous endoscopic gastrostomy (PEG) has been shown to benefit patients with resectable carcinoma of the head and neck. In order to determine whether patients with existing tumor or postresection anatomic changes of the upper respiratory tract can undergo this procedure with an acceptably low complication rate, 349 patients with attempted PEG were studied. The PEG procedure was successful in 114 of 122 carcinoma patients, as compared to 220 of 227 patients in a control group (patients with neurologic disease). Intraoperative complications preventing PEG placement included pharyngeal or esophageal obstruction, inadequate transillumination of the abdominal wall, and respiratory distress and occurred in 7% of carcinoma patients and 3% of controls. The incidence of airway obstruction during endoscopy was equal between groups (1%). Postoperative complications related to the gastrostomy tube were more frequent in the nonhead and neck cancer group (14% versus 5%). Younger age, fewer concomitant medical problems, and better nutritional status may account for this difference. These findings suggest that preoperative, postoperative, and unresectable head and neck cancer patients are appropriate candidates for PEG, and postgastrostomy performance appears superior to that in other patient populations.

Cisplatin, fluorouracil, and leucovorin augmented by interferon alfa-2b in head and neck cancer: a clinical and pharmacologic analysis.

PURPOSE To increase the activity of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) through further biochemical modulation and study the pharmacologic interaction of 5-FU and interferon alfa-2b (IFN). PATIENTS AND METHODS Escalating doses of IFN (0.5 to 4.0 x 10(6) U/m2/d x 6) were added to cisplatin 100 mg/m2, continuous infusion 5-FU 800 or 640 mg/m2/d x 5, and leucovorin 100 mg orally every 4 hours. Forty-eight previously untreated patients with locoregionally advanced head and neck cancer received up to three cycles of PFL-IFN. RESULTS Twenty-one patients were treated during a phase I cohort study. Dose-limiting mucositis was seen with 800 mg/m2/d of 5-FU and 0.5 x 10(6) U/m2/d of IFN. After decreasing the 5-FU dose to 640 mg/m2/d, the maximally tolerated dose (MTD) of IFN was 2.0 x 10(6) U/m2/d. Mucositis and myelosuppression were dose-limiting. Of 34 patients treated at this MTD, 56% (95% confidence interval, 39% to 73%) had a complete remission. There was no correlation between 5-FU clearance and IFN dose. Pharmacodynamic analyses at the MTD showed that older age, female sex, and higher 5-FU area under the time versus concentration curve (AUC) were associated with lower nadir counts and/or increased mucositis. Seven patients with diabetes mellitus had significantly increased myelosuppression, serum creatinine, hypocalcemia, higher 5-FU concentrations, and lower 5-FU clearance compared with nondiabetics. CONCLUSION The recommended doses for PFL-IFN are 640 mg/m2/d for 5-FU and 2.0 x 10(6) U/m2/d for IFN. Sex, age, 5-FU AUC, and diabetes mellitus may have an impact on the pharmacodynamics of this regimen.

Percutaneous endoscopic gastrostomy in the management of head and neck carcinoma

In patients undergoing resection of head and neck malignancies, structural and functional deficits commonly preclude adequate oral nutrition and prolong hospital stay. To address this issue, the benefit of routine preoperative placement of percutaneous endoscopic gastrostomy (PEG) was studied in a group of these patients. The postoperative course of 89 patients undergoing primary resection of advanced (stage III and IV) squamous cell carcinomas of the upper aerodigestive tract was examined. The hospital stay was reduced by up to 61% with PEG compared to hospital stay with standard nasogastric tube (NGT) alimentation. The difference was statistically significant for primary sites involving the larynx and pharynx, but not for lesions of the oral cavity. For tongue base tumors, there was a trend toward reduced hospitalization which did not reach statistical significance. The fistulization rate was unchanged. The complication rate for PEG was 5%, and morbidity was less with PEG than with NGT. The authors recommend the preoperative placement of PEGs for all patients with advanced carcinomas of the larynx, hypopharynx, and oropharynx.

Pharyngeal suspension suture with Repose bone screw for obstructive sleep apnea

OBJECTIVE: Multilevel surgery for obstructive sleep apnea syndrome (OSA) may improve success. This studys goal is to prospectively evaluate the feasibility and short-term subjective effectiveness of a new tongue-suspension technique. METHODS: A multicenter nonrandomized open enrollment trial used the Repose device to treat tongue obstruction in 39 snoring and OSA patients. Outcomes include 1- and 2-month subjective reports of general health, snoring, and sleep. RESULTS: Twenty-three patients completed 1 month and 19 completed 2 months of follow-up. In OSA patients, activity level, energy/fatigue, and sleepiness improved. Two-month outcomes were less (activity level, energy/fatigue, and sleepiness). Fewer changes were observed in snorers than in OSA patients. There were 6 complications (18%), including sialadenitis (4), gastrointestinal bleeding (1), and dehydration (1) after the procedure. CONCLUSION: A pharyngeal suspension suture changes subjective outcomes. Improvement is incomplete. The procedure is nonexcisional, but significant complications may occur. Further evaluation is required to demonstrate effectiveness.