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Purpose Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. Methods and Materials From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. Results Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p = .006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. Conclusions Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated. © 2002 Wiley Periodicals, Inc. Head Neck 24: 236–246, 2002; DOI 10.1002/hed.10017

Conventional radiotherapy alone in treatment of unresectable or locally advanced head and neck cancer has poor results. To improve outcome without significant increase in acute and late morbidity, we began a moderately accelerated hyperfractionation radiation therapy protocol without breaks for treatment of unresectable/advanced head and neck malignancies. From August 1984 to June 1995, 48 patients with unresectable or advanced carcinoma of the head and neck were treated using a protocol of accelerated hyperfractionation radiation therapy at Kaiser Permanente Medical Center, Los Angeles. Patients were treated twice a day using 150 cGy per fraction, 4 days per week, to a final dose of 60 Gy. Two patients were excluded from this analysis because they did not complete treatment. With a median follow-up of 33 months, 31 (67%) patients have had disease recurrence, 30 (65%) of whom had a locoregional component to their failures. At the last follow-up, 12 patients (26%) were alive with no evidence of disease, 30 patients had died of disease, and 4 had died of intercurrent disease without recurrence. Nine (19%) patients required treatment interruptions averaging 8 days in duration. This accelerated regimen resulted in outcomes similar to those with conventional radiotherapy, most likely because of a conservative total dose. Further refinement of fractionation schedules with potential incorporation of chemotherapy must be investigated.