Hypothyroidism after treatment for nonthyroid head and neck cancer.

OBJECTIVES: To determine the incidence of posttreatment hypothyroidism in patients treated with surgery with or without radiotherapy for advanced-stage nonthyroid head and neck cancer and to make recommendations for its detection. DESIGN: A prospective study to assess the incidence and time frame of occurrence of hypothyroidism in patients by primary tumor site and treatment modality. Thyroid function tests were performed preoperatively, at the first postoperative visit, and then approximately every 6 months. Patients were followed up for up to 3 years. SETTING: Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio. PATIENTS: A total of 251 patients with nonthyroid head and neck cancer were originally enrolled; 198 patients with evaluable data were studied to determine the incidence of posttreatment hypothyroidism. Approximately 80% of the patients had advanced stage (III or IV) or recurrent cancer. RESULTS: The overall incidence of posttreatment hypothyroidism was 15% in 198 patients followed up for a mean of approximately 12 months. Hypothyroidism developed in 12% of patients treated with nonlaryngeal surgery and radiotherapy. The group undergoing total laryngectomy (with thyroid lobectomy) and radiotherapy had a 61% incidence of hypothyroidism. The average time to detection of hypothyroidism was 8.2 months. CONCLUSIONS: Approximately 15% of patients treated for advanced head and neck cancer with surgery and radiotherapy will develop hypothyroidism. Those treated with total laryngectomy and radiotherapy are at greatest risk.

Feasibility trial of postoperative radiotherapy and cisplatin followed by three courses of 5-FU and cisplatin in patients with resected head and neck cancer: a Southwest Oncology Group study.

BACKGROUND: Appropriate adjuvant chemotherapy for resected head and neck cancer patients has yet to be defined. Multiple trials have noted trends toward improved disease-free survival and local control. The Southwest Oncology Group undertook a feasibility trial of postoperative cisplatin and radiotherapy followed by three cycles of cisplatin and 5-fluorouracil. METHODS: Patients with resected stage III or IV head and neck cancer received cisplatin, 100 mg/m2, on days 1, 22, and 43 of radiotherapy. This therapy was followed by three cycles of cisplatin, 100 mg/m2 or last tolerated dose, and 5-fluorouracil, 1000 mg/m2, on days 1 to 4 every 21 days. RESULTS: Seventy-two patients from 22 institutions were registered; 68 were evaluable. Sixty-eight patients received radiotherapy. Only 25 of 68 patients (36.7%) were able to complete all six cycles of chemotherapy. Forty-three of 68 patients (63%) completed all three cycles with radiotherapy. Toxicities were tolerable. One toxic death occurred. CONCLUSIONS: It is not feasible to deliver six cycles of chemotherapy postoperatively in the sequence described. Compliance issues need further exploration to define effective adjuvant chemotherapy for head and neck patients.

Intensified regimen for advanced head and neck squamous cell carcinomas.

OBJECTIVE: To devise an intensified treatment regimen for patients with advanced, resectable head and neck squamous cell carcinomas. DESIGN: Phase I/II clinical trial consisting of perioperative cisplatin chemoradiotherapy, surgical resection, intraoperative radiotherapy, and postoperative cisplatin chemoradiotherapy. SETTING: The Ohio State University Comprehensive Cancer Center, Columbus. PATIENTS: Thirty-seven patients (median age, 63 years) with advanced oral cavity, oropharyngeal, or hypopharyngeal carcinomas. RESULTS: The range of time at risk was 1 to 30 months (median, 21 months). Thirty of the 37 registered patients were analyzable; 11 have died (5 with distant metastases; 1 of lung carcinoma; and 5 were cancer-free); 2 experienced second primary tumors in the oral cavity (out of or adjacent to the previous radiotherapy portals). Treatment compliance was excellent (92%), morbidity was low, and excellent locoregional control was achieved. CONCLUSIONS: The initial results are encouraging; the future strategy will intensify the systemic component of therapy based on results from concurrent laboratory studies.

Factors involved in long- and short-term mandibular plate exposure.

OBJECTIVES: To evaluate and to compare rates and timing of exposure of alloplastic mandibular plates by plate type and tissue reconstruction technique. DESIGN: A retrospective review series of 92 consecutive patients for 4 years (mean follow-up, 30 months). SETTING: National Cancer Institute-designated comprehensive cancer center in a freestanding cancer hospital. PATIENTS: Seventy-nine patients received alloplastic mandibular plates for segmental defects, and 13 patients received compression plates for mandibular osteotomies following ablative cancer surgery, including 21 titanium hollow osseointegrating reconstruction, 41 Storz, 16 Synthes, and 5 AO/ASIF (Arbeitsgemein schott fur Ostcosynthese fragen/Association for the Study of Internal Fixation) plates. Primary flap repair was provided by 71 pedicled soft tissue and 19 osseocutaneous free flaps, with primary closure in the remaining 2. INTERVENTION: Most of the reconstructions of the mandibular defect was with an alloplastic plate with musculocutaneous flap or revascularized bone graft. OUTCOME MEASURES: Clinically apparent intraoral or extraoral plate exposure. RESULTS: Plate exposure occurred in 25 cases. Nine plates were exposed extraorally, at a mean postoperative interval of 40 weeks. The remaining 16 plates were exposed intraorally at a mean postoperative interval of 16 weeks. There was no significant difference in the exposure rates of different plate types or methods of reconstruction. The titanium hollow osseointegrating reconstruction plate had a similar exposure rate compared with the other plates. Size and site of the defect were the only significant predictors of plate exposure Radiotherapy and postoperative complications did not affect the rate of exposure. CONCLUSIONS: Extraoral plate exposure occurs less commonly and later in the postoperative period than intraoral exposure, suggesting different causes. Plate type and type of flap reconstruction do not affect the rate of exposure. This may reflect long follow-up.

Chemotherapy as predictor of compliance.

Patient compliance with the increasingly complex adjuvant therapy protocols has always been of concern, particularly in the head and neck cancer population. The Head and Neck Intergroup recently concluded a phase III prospective randomized trial testing the addition of three courses of cisplatinum containing combination chemotherapy to standard treatment defined as surgery and postoperative radiotherapy for advanced stage III and IV squamous cell carcinoma. The chemotherapy was administered following the surgery prior to the postoperative radiotherapy. Variation from protocol is ranked retrospectively as minor acceptable, major acceptable, and major unacceptable. The incidence of major unacceptable variation from the protocol for radiotherapy immediately following the surgery was 15% vs. 19% in the population that completed all three courses of the chemotherapy (P < 0.10). However, for those patients that completed less than the three courses of chemotherapy, the incidence of major unacceptable variation in radiotherapy was 33% (P < 0.001). This observation was controlled for site, stage, performance status, age, sex, surgical margins and experience of participating institution. We conclude that compliance with a multicourse adjuvant chemotherapy regimen is predictive of subsequent compliance to radiotherapy in the head and neck cancer population.

Identifying high-risk patients before head and neck oncologic surgery.

Patients from the Comprehensive Cancer Center of the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, who were undergoing major head and neck oncologic surgery were prospectively studied to determine predictors of postoperative medical complications and wound infection. Of 119 patients studied, 28 (24%) had at least one postoperative medical complication. The strongest predictors of medical complication were poor functional capacity as assessed by the Specific Activity Scale questionnaire and alcohol abuse. Thirteen patients (11%) developed wound infections. The strongest predictors of wound infection were an elevated preoperative platelet count and prolonged surgery. Wound infection was the strongest correlate of prolonged hospital stay. These findings suggest that the Specific Activity Scale questionnaire identifies patients at risk for medical complication, that alcohol abuse should be managed aggressively, and that thrombocytosis identifies patients at risk for wound infection.

Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.

Poorly differentiated ('insular') thyroid carcinoma. Report of two cases and review of the literature.

The clinical, histopathologic, immunohistochemical, and electron microscopic findings of two cases of poorly differentiated ("insular") thyroid carcinoma are reported and compared with the 25 cases previously described in the literature. These 27 cases occurred in eight men and 19 women, aged from 34 to 77 years. All but 2 presented with a thyroid mass. Eleven (41%) of the 27 patients experienced local recurrences following surgery, 17 (63%) had development of cervical lymph node metastases, 5 (19%) had development of mediastinal lymph node metastases, 11 (41%) had pulmonary metastases, and 9 (33%) had bone metastases, and 9 (33%) had bone metastases. At least 15 patients (56%) are known to have died of their disease, usually within 8 years of diagnosis. Pathologically, the tumors are distinctive and grow as solid islands (insulae) of small cells separated by artifactually created clefts. In some instances, small follicles are also noted within the insulae. All tumors were positive on immunostaining for thyroglobulin. In view of the propensity for local recurrences and lymphatic and hematogenous dissemination, a total thyroidectomy and neck dissection would seem advisable. Additionally, adjuvant external beam irradiation, systemic chemotherapy, and/or radioactive iodine therapy should also be considered.

Lidocaine v bupivacaine in facial plastic surgery. A clinical trial.

The ideal local anesthetic agent for facial plastic surgery should have rapid onset, good surgical anesthesia, and reasonably long duration. The purpose of this prospective, randomized, double-blind study was to compare 1% lidocaine hydrochloride with 1:200,000 epinephrine with 0.5% bupivacaine hydrochloride with 1:200,000 epinephrine, a newer, longer-acting local anesthetic, in different facial operations. The results suggest that bupivacaine is an effective and safe agent for these procedures.