Management of the unknown primary in patients with metastatic cancer of the head and neck.

The evaluation of the patient with metastatic cervical lymph node squamous cell carcinoma and an unknown primary tumor frequently involves the use of guided biopsies as a diagnostic tool. This study was performed to assess the effectiveness of these biopsies. Using a retrospective chart review, we identified 25 patients who had undergone a total of 100 guided biopsies to evaluate an unknown primary malignancy of the head and neck. We found that 99 of the 100 biopsies were negative for malignancy. Although guided biopsies were obviously not helpful in these cases, we believe this might be attributable to the fact that the method of performing them is inconsistent among surgeons. Therefore, we present an algorithm for the management of the unknown primary head and neck malignancy, including recommendations regarding the use of guided biopsies.

Postoperative irradiation of minor salivary gland malignancies of the head and neck.

OBJECTIVES: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors. MATERIALS AND METHODS: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years). RESULTS: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted. CONCLUSIONS: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

Tissue oxygen distribution in head and neck cancer patients.

BACKGROUND: The importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been known. METHODS: We evaluated the tissue oxygenation status with a polarographic needle electrode system in 37 patients with malignancies of the head and neck and correlated the pO2 of 25 patients with treatment outcome. RESULTS: Sixteen tumors contained areas of severe hypoxia, defined by pO2 values below 2.5 mm Hg. Tumor oxygenation parameters were not correlated with hemoglobin, age, and history of tobacco use. There were no subcutaneous PO2 values below 10 mm Hg (ie, no areas of moderate or severe hypoxia), whereas this degree of hypoxia was commonly found in the tumors. Though not statistically significant, hypoxic tumors showed trends for poorer treatment outcome. CONCLUSION: Our data demonstrate a great interindividual variability in the oxygenation of head and neck cancers and appears unassociated with clinical parameters. The method is capable of identifying patients with poorly oxygenated tumors, thereby providing important information for selecting patients who might need customized therapy designed to kill hypoxic tumor cells. Hypoxic tumors show a consistent trend for poor treatment outcome.

DNA damage measured by the comet assay in head and neck cancer patients treated with tirapazamine.

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Pretreatment and midtreatment measurement of oxygen tension levels in head and neck cancers.

OBJECTIVE: Considerable evidence exists to suggest that tumor hypoxia results in radioresistance. Historically, it has been difficult to assess tumor oxygen tension levels reliably. These levels can now be assessed in head and neck malignancies using the Eppendorf pO2 histograph, which uses a fine-needle electrode and a computerized micromanipulator. This technology was used to compare the pretreatment tumor oxygen tension level in lymph node metastases of patients with head and neck cancer to measurements taken during nonsurgical treatment after a partial response had been achieved. STUDY DESIGN: Prospective study. METHODS: Oxygen tension levels were measured in the cervical lymph nodes of 10 patients with biopsy-proven head and neck squamous cell carcinoma and cervical metastases who were being treated with nonsurgical management. These levels were obtained using the Eppendorf pO2 histograph system. Measurements were taken before the start of treatment and were repeated when the size of the cervical metastatic node had decreased by 50%. Normal subcutaneous tissue was measured during the same session. The mean and median pO2 levels, as well as the percentage of measurements with pO2 less than 5 mm Hg were determined. RESULTS: A mean of 72.6 measurements per session was taken from each lymph node. The median tumor pO2 measurement fell from a mean (+/-SD) of 13.9+/-8.0 mm Hg to 7.3+/-9.9 mm Hg. Even more dramatic, however, was the substantial increase in the percentage of values less than 5 mm Hg, a rise from 29% to 52%. CONCLUSIONS: While there is variability both in the pretreatment oxygenation of head and neck cervical metastases and in the change in tumor oxygen tension during treatment, there appears to be a decrease in the overall oxygenation of the tumors. The dramatic increase in very low oxygen measurements may reflect selective survival of radioresistant or chemoresistant hypoxic tumor cells. Cells at the very low level would be expected to be radiobiologically hypoxic (resistant to radiation-induced cell kill).

Ambulatory tonsillectomy and adenoidectomy.

The performance of tonsillectomy and adenoidectomy in an ambulatory setting is controversial. However, most current studies show that with adequate criteria for patient selection and careful postoperative observation, these procedures can be safely done as outpatient surgery. This study was undertaken to reassess the safety of outpatient tonsillectomy and adenoidectomy surgery and to reevaluate the current recommendations for postoperative care. A prospective study was undertaken to relate the incidence of significant complications, including hemorrhage, protracted emesis, and fever, to each postoperative hour. The study included 534 pediatric patients (age 14 or less) undergoing tonsillectomy with or without adenoidectomy. All 534 patients were observed for 5 postoperative hours, and 175 of the 534 patients were observed for 6 postoperative hours. To assess complications occurring in the first postoperative week, all attending surgeons involved in this study were asked to anonymously report the occurrence of hemorrhage, protracted emesis, and/or fever from the time of discharge through the seventh postoperative day. In this study, no complications were encountered during the fifth or sixth postoperative hours. These results indicate that it is both safe and appropriate to perform tonsil and adenoid surgery in the ambulatory setting. Furthermore, the current recommendation that patients remain under postoperative recovery room observation for 6 hours appears to be excessive. This observation period may be safely reduced to 4 hours.